United States District Court, D. Delaware
REPORT AND RECOMMENDATION
CHRISTOPHER J. BURKE UNITED STATES MAGISTRATE JUDGE
these consolidated Hatch-Waxman actions filed by Plaintiffs
Astellas Pharma Inc., Astellas Ireland Co., Ltd.
("AICL") and Astellas Pharma Global Development,
Inc. ("APGD" and collectively with other
Plaintiffs, "Astellas" or "Plaintiffs")
against Actavis Elizabeth LLC, Lupin Ltd. and Lupin
Pharmaceuticals, Inc., Zydus Pharmaceuticals (USA), Inc. and
Cadila Healthcare Ltd., Aurobindo Pharma Ltd., Aurobindo
Pharma USA, Inc. and Aurolife Pharma LLC (collectively,
"Aurobindo"), Prinston Pharmaceutical Inc., Sandoz
Inc., Sawai Pharmaceutical Co., Ltd. and Sawai USA, Inc.
(collectively, "Sawai" and together with Aurobindo,
"SA Defendants"), and Apotex Inc. and Apotex Corp.,
Plaintiffs allege infringement by all Defendants
("Defendants") of, inter alia, U.S. Patent
Nos. 7, 342, 117 (the "'117 patent") and 7,
982, 049 (the "'049 patent"). Presently before
the Court is the matter of claim construction. The Court
recommends that the District Court adopt the constructions as
set forth below.
Pharma Inc. is the record owner and assignee of the '117
patent and the '049 patent, and AICL is the exclusive
licensee of the patents. (D.I. 1 at ¶¶ 42-43) APGD
has contracted with Astellas Pharma US, Inc., a subsidiary of
Astellas Pharma Inc., to market and sell the drug mirabegron
under the trade name Myrbetriq®. (Id. at
¶¶ 39, 44) Myrbetriq tablets are indicated for the
treatment of overactive bladder with symptoms of urge urinary
incontinence, urgency, and urinary frequency. (Id.
at ¶ 41)
are in the business of developing, manufacturing and
distributing generic versions of branded drug products
throughout the United States. (See, e.g., Id. at
The'117 and'049 Patents
'117 patent and the '049 patent are both entitled
"α-Form or β-form crystal of Acetanilide
Derivative." (D.I. 1, exs. B, C (hereinafter, the
'"117 patent" and the '"049
patent")) The '049 patent is a continuation of the
U.S. patent application that led to the '117 patent, and
the patents therefore share a specification. (See
'049 patent; D.I. 77 at 2) Both patents claim priority to
PTC Application No. PCT/JP02/11217, filed on October 29,
2002, and to Japanese Patent No. JP2001-332914, filed on
October 30, 2001. ('117 patent; '049 patent; D.I. 77
at 2) The '117 patent issued on March 11, 2008, ('117
patent), and the '049 patent issued on July 19, 2011,
('049 patent). The '117 patent claims crystal forms
of mirabegron, and the '049 patent claims pharmaceutical
compositions comprising crystal forms of mirabegron and a
pharmaceutically acceptable carrier, as well as methods of
treating diabetes utilizing the claimed pharmaceutical
compositions. ('117 patent, col. 12:18-30; '049
patent, cols. 11:5-12:33; D.I. 1 at ¶¶ 27, 30)
can exist in crystalline form, meaning the atoms (or
molecules) are arranged in a repeating and ordered pattern
that extends in three dimensions to form the crystal. (D.I.
78 at ¶ 29; D.I. 97 at ¶ 25) Many compounds
have the ability to crystallize into more than one distinct
crystal form, with the atoms packed differently in the
crystal's structure from form to form; these different
crystalline forms of the same substance are referred to as
polymorphs. (D.I. 78 at ¶ 30; D.I. 97 at ¶ 26) For
example, the molecules of an active pharmaceutical ingredient
("API") may exist in more than one crystalline
form. (D.I. 78 at ¶ 30) Polymorphs of an API may have
differing properties, such as solubility, hygroscopicity,
dissolution rate and chemical and thermal stability.
(Id.) Each new crystal form is generally given a
formal name using sequential Roman numerals, Arabic numerals,
or Greek or Latin letters. (Id. at ¶ 39; D.I.
97 at ¶ 28) Each "Form X" name for a different
polymorph refers to a unique, specific crystalline form
having its own characteristics. (D.I. 78 at ¶¶ 30,
39; D.I. 97 at ¶ 28)
x-ray diffraction (known as "XRPD") is a common
method that has been used for many years in the
pharmaceutical industry to help characterize and distinguish
different crystalline forms. (D.I. 78 at ¶ 31; D.I. 97
at ¶ 30) This method tests a small amount of crystalline
powder (instead of a single crystal) by exposing the sample
to x-rays. (D.I. 78 at ¶ 31) X-ray diffraction results
when x-rays of particular wavelengths are directed at a
sample; the diffraction angles are measured, and an
observable pattern of peaks is created that serves as a
fingerprint for each unique crystal structure. (Id.
at ¶¶ 31-32; D.I. 97 at ¶¶ 30-31, 35)
These patterns of peaks can be placed on a chart, known as an
"x-ray diffraction diagram" or "x-ray
diffractogram," so that all of these peaks (including
those peaks that stand out as being the most intense) can be
viewed at one time. (See, e.g., '049 patent at
FIGS. 1, 3-4; D.I. 97 at ¶ 32)
well-established analytical technique that can be used to
characterize crystal forms is differential scanning
calorimetry ("DSC"). (D.I. 78 at ¶ 40; D.I. 97
at ¶ 40) One property of a polymorph is its melting
point and associated endotherm, which measures the
temperature at which the compound turns from solid to liquid
as well as the heat absorbed during the process. (D.I. 97 at
¶ 40) DSC measures the melting point of a sample by
analyzing the difference in the amount of heat flowing
between two pans sitting on top of two separate heaters-a
sample pan and a reference pan left empty. (D.I. 78 at ¶
41; D.I. 97 at ¶ 40) When a sample melts, energy is
required, and this event is reflected by a peak in the DSC
profile representing the energy required to melt the crystal.
(D.I. 78 at ¶ 42; D.I. 97 at ¶ 40)
litigation arises from each of Defendants' submissions of
Abbreviated New Drug Applications ("ANDAs") to the
United States Food and Drug Administration ("FDA"),
which seek approval to market generic versions of Myrbetriq.
(See, e.g., D.I. 1 at ¶ 45; D.I. 77 at 1) APGD
is the holder of New Drug Application No. 202611, which
covers Myrbetriq. (D.I. 1 at ¶ 39) Plaintiffs filed the
instant cases in October 2016, alleging, inter alia,
that Defendants' AND A products and the use thereof would
infringe at least claim 1 of the '117 patent and certain
claims of the '049 patent pursuant to 35 U.S.C. §
271(a), and that Defendants' submission of their AND As
constituted acts of infringement of certain claims of the
'049 patent pursuant to 35 U.S.C. § 271(e)(2).
(See, e.g., D.I. 1 at ¶¶ 57,
August 10, 2017, Judge Joseph F. Bataillon referred "all
dispositive and nondispositive matters on all issues,
including claim construction, except for summary judgments,
Daubert motions and pretrial motions in limine" to the
Court. (D.I. 67) The parties completed lengthy briefing on
claim construction on March 21, 2018. (D.I. 77, 93, 95, 112,
146, 148, 155, 156) The Court held a Markman hearing
on March 23, 2018. (D.I. 163 (hereinafter, "Tr."))
The Scheduling Order states that the Court "shall issue
its decision on claim construction on or before June 20,
2018." (D.I. 25 at 9 (emphasis omitted))
STANDARD OF REVIEW
well-understood that "[a] claim in a patent provides the
metes and bounds of the right which the patent confers on the
patentee to exclude others from making, using, or selling the
protected invention." Corning Glass Works v.
Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1257 (Fed.
Cir. 1989). Claim construction is a generally a question of
law, although subsidiary fact finding is sometimes necessary.
Teva Pharms. USA, Inc. v. Sandoz, Inc., 135 S.Ct.
831, 837-38 (2015).
Court should typically assign claim terms their
'"ordinary and customary meaning[, ]'"
which is "the meaning that the term[s] would have to a
person of ordinary skill in the art ['POSA'] in
question at the time of the invention, i.e., as of the
effective filing date of the patent application."
Phillips v. AWHCorp., 415 F.3d 1303, 1312-13 (Fed.
Cir. 2005) (citations omitted). However, when determining the
ordinary meaning of claim terms, the Court should not extract
and isolate those terms from the context of the patent, but
rather should endeavor to reflect their "meaning to the
ordinary artisan after reading the entire patent."
Id. at 1321; see also Eon Corp. IP Holdings LLC
v. Silver Spring Networks, Inc., 815 F.3d 1314, 1320
(Fed. Cir. 2016).
proceeding with claim construction, the Court should look
first and foremost to the language of the claims themselves,
because "[i]t 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, 415 F.3d at 1312 (internal quotation marks
and citations omitted). For example, the context in which a
term is used in a claim may be "highly
instructive." Id. at 1314. In addition,
"[o]ther claims of the patent in question, both asserted
and unasserted, can ... be valuable" in discerning the
meaning of a particular claim term. Id. This is
"[b]ecause claim terms are normally used consistently
throughout the patent, [and so] the usage of a term in one
claim can often illuminate the meaning of the same term in
other claims." Id. Moreover, "[differences
among claims can also be a useful guide [, ]" as when
"the presence of a dependent claim that adds a
particular limitation gives rise to a presumption that the
limitation in question is not present in the independent
claim." Id. at 1314-15.
addition to the words of the claims, the Court should look to
other intrinsic evidence. For example, the Court should
analyze the patent specification, which "may reveal a
special definition given to a claim term . .. that differs
from the meaning [that term] would otherwise possess" or
may reveal an intentional disclaimer of claim scope.
Id. at 1316. Even if the specification does not
contain such revelations, it "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." Id. at 1315 (internal quotation
marks and citation omitted). That said, however, the
specification "is not a substitute for, nor can it be
used to rewrite, the chosen claim language."
SuperGuide Corp. v. DirecTV Enters., Inc., 358 F.3d
870, 875 (Fed. Cir. 2004). And a court should also consider
the patent's prosecution history, if it is in evidence,
because it "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[.]" Phillips, 415
F.3d at 1317.
evidence, "including expert and inventor testimony,
dictionaries, and learned treatises [, ]" can also
"shed useful light on the relevant art[.]"
Id. (internal quotation marks and citations
omitted). Overall, while extrinsic evidence may be useful, it
is "less significant than the intrinsic record in
determining the legally operative meaning of claim
language." Id. (internal quotation marks and
citations omitted); accord Markman v. Westview
Instruments, Inc., 52 F.3d 967, 981 (Fed. Cir. 1995).
utilizing these resources during claim construction, courts
should keep in mind that "[t]he construction that stays
true to the claim language and most naturally aligns with the
patent's description of the invention will be, in the
end, the correct construction." Renishaw PLC v.
Marposs Societa'per Azioni, 158 F.3d 1243, 1250
(Fed. Cir. 1998).
U.S.C. § 112 ("Section 112") requires that a
patent claim "particularly point out and distinctly
claim the subject matter which the applicant regards as his
invention." 35 U.S.C. § 112, ¶
If it does not, the claim is indefinite and therefore
invalid. Nautilus, Inc. v. Biosig Instruments, Inc.,
134 S.Ct. 2120, 2125 (2014) ("Nautilus").
In Nautilus, the Supreme Court of the United States
set out the test to be applied in the definiteness inquiry:
"a patent is invalid for indefiniteness if its claims,
read in light of the specification delineating the patent,
and the prosecution history, fail to inform, with reasonable
certainty, those skilled in the art about the scope of the
invention." Id. at 2124. Definiteness is to be
evaluated from the perspective of a POSA at the time the
patent was filed. Id. at 2128.
claim construction, definiteness is a question of law for the
court. H-WTech, L.C. v. Overstock.com, Inc., 758
F.3d 1329, 1332 (Fed. Cir. 2014); Pi-NetInt'l Inc. v.
JPMorgan Chase & Co., 42 F.Supp.3d 579, 586 (D. Del.
2014). The United States Court of Appeals for the Federal
Circuit has stated that "[a]ny fact critical to a
holding on indefiniteness ... must be proven by the
challenger by clear and convincing evidence." Intel
Corp. v. VIA Techs., Inc., 319 F.3d 1357, 1366 (Fed.
Cir. 2003); see also Tech. Licensing Corp. v. Videotek,
Inc., 545 F.3d 1316, 1338 (Fed. Cir.
primary purpose of the definiteness requirement is to ensure
that patent claims are written in such a way that they give
notice to the public of what is claimed, thus enabling
interested members of the public (e.g., competitors of the
patent owner) to determine whether they infringe. All
Dental Prodx, LLC v. Advantage Dental Prods., Inc., 309
F.3d 774, 779-80 (Fed. Cir. 2002). Put another way, "[a]
patent holder should know what he owns, and the public should
know what he does not." Festo Corp. v. Shoketsu
Kinzoku Kogyo Kabushiki Co., Ltd., 535 U.S. 722, 731
(2002). Even so, the Supreme Court has recognized that
"absolute precision is unattainable" and not
required. Nautilus, 134 S.Ct. at 2129.
Court takes up the three sets of disputed terms in the order
in which the parties addressed them at the Markman
"α-form crystal" and "β-form
claim term "α-form crystal" appears in claim
1 of the '049 patent, and the claim term
"β-form crystal" appears in claim 3 of that
patent. Claims 1 and 3 are reproduced below:
1. A solid pharmaceutical composition comprising the
α-form crystal of
ethyl] acetanilide and a pharmaceutically acceptable carrier.
('049 patent, col. 11:5-8 (emphasis added))
3. A solid pharmaceutical composition comprising the
β-form crystal of
and a pharmaceutically acceptable carrier.
(Id., col. 11:14-17 (emphasis added))
explain that the terms "α-form crystal" and
"β-form crystal" are "the names of the
two novel crystal forms of mirabegron that are described in
the specification" of the '049 patent. (D.I. 77 at
10) Defendants agree on this point, characterizing the terms
as "arbitrary identifiers given to polymorphs of a given
compound." (D.I. 93 at 12) With respect to the proper
constructions of these claim terms, Plaintiffs propose that
"α-form crystal" be construed to mean
"α-form crystal which is a term of reference for a
polymorphic crystal form of (R)
hydroxy-2-phenylethyl)amino]ethyl]acetanilide that can be
distinguished from other forms." (D.I. 77 at 10)
Likewise, as to "β-form crystal," Plaintiffs
propose that the term be construed to mean "β-form
crystal which is a term of reference for a polymorphic
crystal form of (R) 2-(2-aminothiazol-4-yl)-4'-[2-[(2
hydroxy-2-phenylethyl)amino] ethyl] acetanilide that can be
distinguished from other forms." (Id.)
their part, Defendants assert that the terms are indefinite.
(D.I. 93 at 12) Defendants contend that since these terms do
not have ordinary or customary meanings, the specification of
the '049 patent must provide sufficient data that would
allow the POSA to actually identify each form. (Id.
at 12-13) According to Defendants, the specification fails to
do so. (Id.) Instead, Defendants contend that the
"minimal descriptions" of each form of crystal in
the specification "are often inconsistent and
contradictory" and thus cannot be used to determine
whether a sample falls within the scope of the α-form
or β-form crystal. (Mat 13; see also D.I. 146
at 4; Defendants' Claim Construction Arguments
Presentation, Slides A9-A10) As for Plaintiffs' proposed
constructions, Defendants point out that Plaintiffs'
proposals fail to actually identify any further
characteristics of the α-form and β-form crystals,
and therefore just "[c]onfirm [that] the [t]erms [a]re
[i]ndefmite[.]" (D.I. 93 at 15; Tr. at 30
(Defendants' counsel explaining that Plaintiffs'
proposed construction for "α-form crystal[,
]" for example, essentially states that the "alpha
form means alpha form"))
the Court addresses the key issues raised by the parties'
Why Plaintiffs' Proposed Constructions Are Not
Court finds that Plaintiffs' proposed constructions for
the terms "α-form crystal" and
"β-form crystal" are problematic. This is
because, as Defendants point out, the constructions do not
provide any further clarification as to how the two terms can
be distinguished from each other. (D.I. 93 at
argue that their proposed constructions are sufficient
because: (1) once a new crystalline form has been identified
and described, it will have a "chemical structure and a
host of physical characteristics that can be used to identify
it"; but (2) a POSA would find it unnecessary to recite
all of these characteristics in order to identify the forms,
since the POSA could make that identification simply by
hearing the name for the form. (D.I. 77 at 13; Tr. at 61
(Plaintiffs' counsel contending that, if the claims used
the word "mirabegron," for instance, that is just a
name, but the name "tells you exactly what the thing is,
because from the patent or from other sources, there's
lots of identifying information that tells you what
mirabegron is")) The problem with Plaintiffs position,
however, is that we have a fundamental dispute here
about the terms-i.e., whether there is sufficient guidance in
the intrinsic record to allow the POSA to distinguish the
α-form crystal and β-form crystal from each other
(and if so, what is that guidance)? Were the Court to simply
adopt Plaintiffs' proposed constructions, this would not
resolve the dispute. See, e.g., Celgene Corp. v. Natco
Pharma Ltd., Civil Action No. 10-5197 (SDW), 2014 WL
2196941, at *4 (D.N.J. May 27, 2014) (rejecting plaintiffs
proposal to construe "Form A" to mean "a
polymorphic form of 3-(4-amino-l-oxo-1, 3
dihydro-insoindol-2-yl)piperidine-2, 6-dione that can be
distinguished from other forms" because such a
construction would "give no meaning to the term
'Form A'" and would "ignore the specific
attributes of Form A as defined in the specification").
If the intrinsic record does in fact provide such guidance,
then the constructions for these terms should at least make
reference to that guidance. If the record provides no such
guidance, that would indicate that the terms are
Is There Sufficient Evidence in the Intrinsic Record that Can
Be Used to Distinguish These Two Crystal Forms from Each
Other, so as to Avoid Indefiniteness Concerns (and if so,
What Is It)?
concluded that Plaintiffs' proposed constructions will
not be helpful here, the Court next examines whether the
intrinsic record contains sufficient evidence that can be
used to teach a POSA, with reasonable certainty, how to
distinguish these two different crystal forms from each
other? In Plaintiffs' view, "the
common specification of the [asserted patents] discloses to a
POSA how to identify and distinguish the a-form and ]3-form
crystals of mirabegron." (D.I. 112 at 3; see
also D.I. 155 at 9 (explaining that Plaintiffs "do
not argue that the term 'α-form crystal' or
'(β-form crystal' have a meaning independent of
and apart from the '117 and '049 Patent
'049 patent's specification does expressly discuss
observed properties of the α-form crystal and (3-form
crystal. Plaintiffs point to the following supporting data
described in the ...