SUPERNUS PHARMACEUTICALS, INC. v. ZYDUS PHARMACEUTICALS (USA) INC. et al
Filing
127
OPINION. Signed by Judge Susan D. Wigenton on 3/9/16. (cm )
NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF NEW JERSEY
SUPERNUS PHARMACEUTICALS, INC.,
Civil Action No. 14-06102
(SDW) (LDW)
Plaintiff,
(Consolidated with
Civil Action No. 14-07272)
v.
ACTAVIS INC., et al.,
MARKMAN OPINION
Defendants.
March 9, 2016
SUPERNUS PHARMACEUTICALS, INC.,
Plaintiff,
v.
ZYDUS PHARMACEUTICALS (USA) INC.,
et al.,
Defendants.
WIGENTON, District Judge.
Before the Court are the briefs and supporting materials of Plaintiff Supernus
Pharmaceuticals, Inc. (“Plaintiff”) and Defendants Actavis, Inc., Actavis Laboratories FL, Inc.,
Actavis Pharma, Inc., Watson Laboratories, Inc., ANDA, Inc., and Actavis plc k/n/a Allergan plc
(collectively, “Actavis”), and Zydus Pharmaceuticals (USA) Inc. and Cadila Healthcare Limited
(collectively, “Zydus”) (Actavis and Zydus hereafter collectively referred to as “Defendants”)
regarding the request for a patent claim construction pursuant to Local Patent Rule 4.5(a).
1
This Court has jurisdiction over this action pursuant to 28 U.S.C. §§ 1331 and 1338(a).
Venue is proper under 28 U.S.C. §§ 1391(b) and 1400(b). This Court held a Markman 1 hearing
on February 3, 2016 regarding patent claims in Plaintiff’s U.S. Patent Nos. 8,298,580 (“the ’580
patent”), 8,663,683 (“the ’683 patent”), 8,877,248 (“the ’248 patent”), 8,889,191 (“the ’191
patent”), and 8,992,989 (“the ’989 patent”) (collectively, “the patents in suit”). After carefully
considering the parties’ written and oral arguments regarding seven claim terms in the patents in
suit, this Court has construed the disputed claim terms as discussed below.
I.
PROCEDURAL AND FACTUAL HISTORY 2
This matter relates to five of Plaintiff’s patents relating to topiramate extended release
capsules, a drug product indicated for initial monotherapy for patients with partial onset seizures
and primary generalized tonic-clonic seizures, and as an adjunctive therapy for patients with partial
onset seizures, primary generalized tonic-clonic seizures, and seizures associated with LennoxGastaut syndrome. Each of Plaintiff’s five patents is titled “Sustained-release formulations of
topiramate” and claims pharmaceutical compositions of topiramate for once-a-day oral
administration, comprising a sustained release component and an optional immediate release
component, the compositions of which can be selectively adjusted to release the active ingredient
along a pre-determined release profile.
Plaintiff’s branded product—Trokendi XR®—is an
extended release capsule with topiramate as its active ingredient.
Plaintiff asserts that Defendants have infringed or will infringe the patents in suit by filing
abbreviated new drug applications (“ANDAs”) with the United States Food and Drug
Administration seeking approval to market generic versions of Trokendi XR®. Defendants
1
2
Markman v. Westview Instruments Inc., 52 F.3d 967 (Fed. Cir. 1995).
Unless otherwise noted, the facts are taken from the parties’ submissions.
2
contend that the products proposed in their ANDAs will not infringe asserted claims of the patents
in suit and/or that the asserted claims are invalid.
Plaintiffs commenced this lawsuit on October 1, 2014, and filed an Amended Complaint
on April 28, 2015. Plaintiff asserted the following six Counts in the Amended Complaint: (I)
infringement of the ’576 Patent (no longer asserted against any Defendant); (II) infringement of
the ’580 Patent; (III) infringement of the ’683 Patent; (IV) infringement of the ’248 Patent; (V)
infringement of the ’191 Patent; and (VI) infringement of the ’989 Patent. (Am. Compl. ¶¶ 53142.) On April 16, 2015, Magistrate Judge Mannion issued an Order consolidating the “topiramate
extended release capsule” cases together. 3
II.
LEGAL STANDARD
Patent claim construction is a matter of law for the court.
Markman v. Westview
Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir. 1995). During interpretation of a claim, courts
should initially look to intrinsic evidence, namely “the patent claims, the specification and the
prosecution history if in evidence.” Bristol-Myers Squibb Co. v. Immunex Corp., 86 F. Supp. 2d
447, 448 (D.N.J. 2000). “[I]ntrinsic evidence is the most significant source of the legally operative
meaning of disputed claim language.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582
(Fed. Cir. 1996). “The court should presume that the terms in the claim mean what they say, and,
unless otherwise compelled, give full effect to the ordinary and accustomed meaning of claim
terms.” Bristol-Myers Squibb Co., 86 F. Supp. 2d at 448. A person of ordinary skill in the art “is
deemed to read the claim term . . . in the context of the entire patent.” Phillips v. AWH Corp., 415
F.3d 1303, 1313 (Fed. Cir. 2005); see Medrad, Inc. v. MRI Devices Corp., 401 F.3d 1313, 1319
(Fed. Cir. 2005) (“We cannot look at the ordinary meaning of the term . . . in a vacuum. Rather,
3
The lead case is 14-cv-06102 and the member case is 14-cv-07272. Another member case, 15-cv-00326, was settled
on October 16, 2015.
3
we must look at the ordinary meaning in the context of the written description and the prosecution
history.” (citation omitted)); see also Markman, 52 F.3d at 979.
If the intrinsic evidence alone will not resolve the ambiguity, the Court may rely on
extrinsic evidence, which includes expert testimony, treatises, dictionaries and articles. BristolMyers Squibb Co., 86 F. Supp. 2d at 448-49. Extrinsic evidence may not be used to vary or
contradict the meaning established by the intrinsic evidence. Phillips, 415 F.3d at 1318-19, 1324.
“The construction that stays true to the claim language and most naturally aligns with the patent’s
description of the invention will be . . . the correct construction.” Id. at 1316.
A key aspect of claim construction is to assist the jury in understanding complicated
language and concepts. See Encap LLC v. Oldcastle Retail, Inc., No. 11-cv-808, 2012 WL
2339095, at *9 (E.D. Wis. June 19, 2012) (“Claim construction is not intended to allow for
needless substitution of more complicated language for terms easily understood by a lay jury.”);
see also C.R. Bard, Inc. v. U.S. Surgical Corp., 388 F.3d 858, 863 (Fed. Cir. 2004) (“[M]erely
rephrasing or paraphrasing the plain language of a claim by substituting synonyms does not
represent genuine claim construction.”); AFG Indus., Inc. v. Cardinal IG Co., Inc., 239 F.3d 1239,
1247 (Fed. Cir. 2001) (“It is critical for trial courts to set forth an express construction of the
material claim terms in dispute, in part because the claim construction becomes the basis of the
jury instructions, should the case go to trial. It is also the necessary foundation of meaningful
appellate review.” (citation omitted)).
III.
PERSON OF ORDINARY SKILL IN THE ART
Claims are construed from the vantage point of a person of ordinary skill in the art
(“POSA”) at the time of the invention. Phillips, 415 F.3d at 1313. Thus, before the Court reviews
the bounds of the claims in light of the specification, it must establish the level of skill that a POSA
4
possessed at the time of the invention. AllVoice Computing PLC v. Nuance Commc’ns, Inc., 504
F.3d 1236, 1240 (Fed. Cir. 2007).
A POSA, as a person of ordinary skill, is “also a person of ordinary creativity.” See KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007). A POSA is “presumed to be one who thinks
along the line of conventional wisdom in the art and is not one who undertakes to innovate.”
Standard Oil Co. v. Am. Cyanamid Co., 774 F.2d 448, 454 (Fed. Cir. 1985). In contrast, a
multidisciplinary “drug team[],” including scientists, medical doctors, economists, and marketing
personnel, (Thakker Resp. Decl. Ex. 13 (Mayersohn Tr. 26:6-28:18)), would be innovative and
more than ordinarily creative. This District has previously “reject[ed] the notion that the ‘person’
of ordinary skill must possess all of the attributes of a multi-member team.” Otsuka Pharm. Co.
v. Sandoz, Inc., Otsuka Pharm. Co. v. Sandoz, Inc., No. 3:07-CV-01000, 2010 WL 4596324, at *9
(D.N.J. Nov. 15, 2010) (Cooper, J.), aff’d, 678 F.3d 1280 (Fed. Cir. 2012). Defendants’ position
that a POSA is “one or more of, or a team including, a Ph.D. or [] M.D., having three or more
years of industrial experience (or a comparable level of additional research and/or laboratory
experience in academia), or alternatively, a Bachelor’s or Master’s Degree and a commensurately
greater number of years of experience in the appropriate field” at the time of the invention, (Defs.’
Op. Br. 2-3), 4 however, runs counter to the generally accepted definition of a POSA. This Court
will, for the purposes of this suit, define a POSA as someone who, at the time of the invention, had
“at least a Bachelor of Science degree in Pharmaceutical Sciences or a related field, approximately
3-5 years of experience in drug delivery technology or a related field, and working knowledge
regarding pharmacokinetics (or . . . commensurate education and experience).” (Pl.’s Op. Br. 5.)
4
For the purposes of this Opinion, “Pl.’s Op. Br.” refers to Plaintiff’s Opening Claim Construction Brief (Dkt. No.
88), “Defs.’ Op. Br.” refers to Defendants’ Opening Claim Construction Brief (Dkt. No. 91), “Pl.’s Resp. Br.” refers
to Plaintiff’s Responding Claim Construction Brief (Dkt. No. 112), and “Defs.’ Resp. Br.” refers to Defendants’
Responding Claim Construction Brief (Dkt. No. 113).
5
IV.
CLAIM CONSTRUCTIONS
The parties dispute the meanings of seven claim terms or phrases with respect to the patents
in suit. 5 The disputed terms are: (1) “at least two different extended release topiramate-containing
components”; (2) “population[s] of beads”; (3) “coating material”; (4) “release controlling
coating”; (5) “a maximum steady state plasma concentration (Cmax) of topiramate”; (6) “a relative
steady state AUC”; and (7) “the same amount of topiramate administered as an immediate release
formulation BID.”
A. “at least two different extended release topiramate-containing components”
Plaintiff’s Proposed
Construction
at least two extended release
topiramate-containing
components, wherein each
component has its own in
vitro rate of drug release
Defendants’ Proposed
Construction
at least two different
extended release topiramatecontaining components
having different compositions
and release rates for
topiramate, within normal
variation
Court’s Construction
at least two extended release
topiramate-containing
components having different
in vitro release rates for
topiramate
For the reasons discussed below, this Court defines “at least two different extended release
topiramate-containing components” as used in claim 1 of the ’580 patent to mean “at least two
extended release topiramate-containing components having different in vitro release rates for
topiramate.”
The parties agree, and the intrinsic evidence supports, that the “at least two different
extended release topiramate-containing components” are defined, at least in part, by having their
own in vitro rate of drug release. (Pl.’s Op. Br. 6, Defs.’ Op. Br. 5.) However, to the extent that
the words “its own” in Plaintiff’s construction could allow components to have the same
properties, this Court adopts the “different” language of the original claim, (’580 patent, claim 1),
5
Two other terms previously in dispute have been withdrawn. (Defs.’ Op. Br. 1.)
6
with respect to the “in vitro release rates” so as to give effect to all terms in the claim and not read
out the express requirement in the claim that the at least two extended release components be
“different.” See Bicon, Inc. v. Straumann Co., 441 F.3d 945, 950 (Fed. Cir. 2006).
The parties also disagree as to (1) whether the two different extended release topiramatecontaining components must also have different compositions, and (2) whether the claim
construction should explicitly state that a single component may have a degree of “normal
variation” 6 in its composition and release rate arising from the inherent variations that occur during
normal manufacturing and testing.
On the first issue, Defendants characterize structural changes that occur due to changes in
process parameters during manufacture as compositional changes, and this leads them to argue
that the patent specification 7 teaches only one way to change the release rate of an extended release
component as required by claim 1, which is changing the composition. In fact, the specification
teaches multiple ways to change the release rate. This Court finds that a POSA would interpret
composition as “the ingredients that go into the final product and must remain in the final product.”
(Byrn Reply Decl. ¶ 17 (citing FDA GUIDANCE FOR INDUSTRY: DRUG PRODUCT at 6, lines 23839).) Thus, a POSA would understand the language of claim 1 to mean that changing any one of
the listed variables (“the nature of the coating, coating level, type of concentration of a pore former,
[and] process parameters” (’580 patent, 7:16-18)) could change the rate of release without
changing the final composition of the component. For this reason, “different compositions” is a
narrower requirement than that required by claim 1, which is different release rates.
6
Defendants also seek to add the “within normal variation” limitation to another claim term, “population[s] of
beads,” infra Part IV.B.
7
All references made to the specification of the patents in suit in this Opinion are made to that of the ’580 patent.
Because the patents in suit are continuations of the same patent application, each of their specifications contains
identical language.
7
Moreover, Defendants’ argument for the “different compositions” limitation rests entirely
on the contention that different compositions are required to change release rates. Even assuming,
arguendo, that this contention is correct, the “different compositions” requirement is unnecessary
because both the original claim language and this Court’s construction already require different
release rates. This Court will not add a limitation to the claims that is not required by the
specification. See Renishaw PLC v. Marposs Societa’ Per Azioni, 158 F.3d 1243, 1249 (Fed. Cir.
1998).
The Court’s construction is supported by other sections of the specification as well. The
titles of Tables 2 and 3 refer to “Topiramate Bead Compositions” and do not list process
parameters, such as the curing temperature or method, whereas the title of Table 1 refers to
“Compositions and process Parameters” and includes process parameters in the body of the table.
Adopting Defendants’ “composition” language would render the “process [p]arameters” language
of the title of Table 1 redundant. Even if, for the sake of argument, the POSA would understand
“composition” to include process parameters, the Federal Circuit held in Phillips that “the
specification may reveal a special definition given to a claim term by the patentee that differs from
the meaning it would otherwise possess. In such cases, the inventor’s lexicography governs.”
Phillips, 415 F.3d at 1316. The Phillips court further stated that the specification is “the single
best guide to the meaning of a disputed term and . . . acts as a dictionary when it expressly defines
terms used in the claims or when it defines terms by implication.” Id. at 1321 (citing Vitronics, 90
F.3d at 1582; Irdeto Access, Inc. v. Echostar Satellite Corp., 383 F.3d 1295, 1300 (Fed. Cir. 2004))
(internal quotation marks omitted). Here, a comparison of the table titles in the specification makes
it clear that the inventors did not intend “composition” to include process parameters. Therefore,
this lexicography will govern.
8
On the second issue, both sides agree that a POSA would not describe something as being
different if it was “within normal variation.” (Byrn Reply Decl. ¶ 31, Park Decl. ¶ 35.) Thus, the
limitation is unnecessary and adding it would create a source of ambiguity. For these reasons, and
because the specification does not mention “within normal variation,” this Court declines to adopt
the “within normal variation” language for any of the claim terms in dispute.
B. “population[s] of beads”
Plaintiff’s Proposed
Construction
population[s] of particles,
spheres, beads, granules,
pellets, particulates or any
structural units that may be
incorporated into an oral
dosage form
Defendants’ Proposed
Construction
multiple structural units with
the same composition and
rate of release, within normal
variation
Construction of “population”
is not necessary. The term
has its plain and ordinary
meaning, e.g., group,
collection, or class.
Court’s Construction
population[s] of particles,
spheres, beads, granules,
pellets, particulates or any
structural units that may be
incorporated into an oral
dosage form
Construction of “population”
is not necessary. The term
has its plain and ordinary
meaning, e.g., group,
collection, or class.
Plaintiff and Defendants disagree on the meaning of “population[s] of beads” as used in
claims 1 and 15 of the ’683 patent, claim 2 of the ’248 patent, claim 1 of the ’191 patent, and claim
2 of the ’989 patent. As this Court has already declined to adopt the “within normal variation”
language, the remaining two points of disagreement are the constructions of “population[s]” and
“beads.” For the reasons discussed below, this Court declines to construe “populations[s],” and
adopts the definition of “beads” contained in the specification.
The specification does not assign a special meaning to the word “population.” “In the
absence of an express intent to impart a novel meaning to claim terms, an inventor’s claim terms
take on their ordinary meaning.” Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1325 (Fed.
9
Cir. 2002). Defendants argue that the plain and ordinary meaning fails to provide any guidance
about what constitutes a “population” of beads, and theoretically permits all beads in a capsule—
even if there are both immediate release and extended release beads—to constitute a single bead
population. (Defs.’ Op. Br. 12.)
However, when beads in a population have particular
characteristics, the claims identify those characteristics. For example, claim 1 of the ’683 patent
and claim 1 of the ’191 patent characterize each bead population “[comprising] an extended release
(XR) component” as having “its own release controlling coating” and “its own rate of release.”
Thus, while Defendants’ “multiple structural units” language has no basis in the intrinsic evidence,
the plain language meaning of “population[s]” is supported by the specification in conjunction
with the guidance of Teleflex, 299 F.3d at 1325. Therefore, this Court declines to construe
“populations[s]” and gives the term its plain and ordinary meaning.
For the term “beads,” the specification provides an explicit definition: “The term ‘beads,’
as used herein, includes, without any limitations on the nature and size thereof, any particles,
spheres, beads, granules, pellets, particulates or any structural units that may be incorporated into
an oral dosage form.” (’580 patent, 4:40-43.) As discussed above, when the specification reveals
a special definition given to a claim term by the patentee that differs from the meaning it would
otherwise possess, the inventor’s lexicography will govern. Phillips, 415 F.3d at 1316. Moreover,
Defendants in their own brief do not contest that their “proposed construction incorporates the
phrase ‘structural units’ to be inclusive of ‘particles, spheres, beads, granules, pellets, particulates
or any structural units,’” and that “there does not appear to be a dispute between the parties with
respect to that aspect of the construction.” (Defs.’ Op. Br. 10.) For these reasons, this Court gives
“beads” its definition from the specification.
C. “release controlling coating”
10
Plaintiff’s Proposed
Construction
a coating that modifies and
controls the release of the
active ingredient
Construction of “coating” is
not necessary. The term has
its plain and ordinary
meaning, e.g., a covering.
Defendants’ Proposed
Construction
a layer of material coated
onto a core or other layer that
modifies and controls the
extended release of the active
ingredient
Court’s Construction
a coating that modifies and
controls the release of the
active ingredient
Construction of “coating” is
not necessary. The term has
its plain and ordinary
meaning, e.g., a covering.
Plaintiff and Defendants disagree on the meaning of “release controlling coating” as used
in claim 1 of the ’580 patent, claims 9 and 12 of the ’683 patent, claims 1 and 14 of the ’248 patent,
claims 7 and 21 of the ’191 patent, and claims 1, 14, 15, and 18 of the ’989 patent. Defendants
admit that the term means that the coating “modifies and controls the release of the active
ingredient,” and this corresponds to the definition of the term found in the specification. (Defs.’
Op. Br. 18.) Therefore, the only point of disagreement is whether “coating” requires construction,
and, if so, how it should be construed. Defendants argue that “coating” requires “a layer of material
coated onto a core or other layer.” However, both “coated onto” and “core or other layer” are
limitations unsupported by the intrinsic evidence, and, for the reasons discussed below, this Court
rejects both limitations.
The phrase “coated onto” appears to require the active application of a coating, whereas a
POSA at the time of the invention would have understood that a coating can be created by other
means, such as microencapsulation. 8 Indeed, two texts that Defendants rely on to support their
proposed construction, (Joint Claim Construction at C7), both describe and discuss
microencapsulation as an established method of coating. (Byrn Decl. ¶ 54, citing HOWARD C.
8
Microencapsulation involves mixing the material to be encapsulated into a solution containing the encapsulating
material and then adding a polymer concentrating agent, which forms a film or coat around the particles, resulting in
coated microcapsules. (Byrn Decl. ¶ 54.)
11
ANSEL
ET AL.,
PHARMACEUTICAL DOSAGE FORMS & DRUG DELIVERY SYSTEMS 232-33 (7th ed.
1999) and 3 HERBERT A. LIEBERMAN ET AL., PHARMACEUTICAL DOSAGE FORMS, TABLETS 77, 161
(2d ed. 1990).) Because “coated onto” requires a limitation not required by the specification, this
Court declines to adopt it. See Renishaw, 158 F.3d at 1249.
The specification’s explicit definition of “release controlling coating” reads: “. . . at least
one population of beads coated with a coating that modifies and controls the release of topiramate
from the beads (release controlling coating).” (’580 patent, 6:39-42.) As this definition requires
the beads to be coated, “core or other layer” unnecessarily narrows the scope of that definition.
See Phillips, 415 F.3d at 1321 (teaching that “the specification acts as a dictionary when it
expressly defines terms used in the claims or when it defines terms by implication”). In addition,
although the specification only discloses embodiments in which the release controlling coating is
coated onto a core or other layer, “it is improper to read limitations from a preferred embodiment
described in the specification—even if it is the only embodiment—into the claims absent a clear
indication in the intrinsic record that the patentee intended the claims to be so limited.” LiebelFlarsheim Co. v. Medrad, Inc., 358 F.3d 898, 913 (Fed. Cir. 2004). Such a “clear indication” does
not exist here. Therefore, this Court declines to adopt the “core or other layer” language.
12
D. “coating material”
Plaintiff’s Proposed
Construction
a material that modifies and
controls the release of the
active ingredient and is
capable of forming a coating
Defendants’ Proposed
Construction
a material coated onto a core
or other layer
Court’s Construction
Construction of “coating
material” is not necessary.
The term has its plain and
ordinary meaning, e.g., a
material used as a covering.
Construction of “coating” is
not necessary. The term has
its plain and ordinary
meaning, e.g., a covering.
Plaintiff and Defendants disagree on the meaning of “coating material” as used in claim 1
of the ’580 patent, claims 9 and 12 of the ’683 patent, claims 1 and 14 of the ’248 patent, claims 7
and 21 of the ’191 patent, and claims 1, 14, 15, and 18 of the ’989 patent. The dispute between
the parties regarding the construction of “coating material” centers on the following three issues:
(1) whether the “coating material” must be a coating or just capable of forming a coating, (2)
whether the range of potential substrates is limited to “a core or other layer,” and (3) whether the
coating material must be “coated onto” the substrate, thus permitting only active application as a
method of applying the coating material. This Court declines to adopt the “core or other layer”
and “coated onto” language for the reasons stated in Part IV.C. Thus, the only remaining point of
disagreement is whether the “coating material” must be a coating or just capable of forming a
coating. For the reasons discussed below, this Court finds that a “coating material” must be a
coating, and gives the term its plain and ordinary meaning, e.g., a material used as a covering.
The specification demonstrates that the patentees did not intend to define a “coating
material” solely by the chemical identity of the excipient in question (regardless of its function in
the formulation), but instead intended for that term to include only those materials that are actually
used in coatings.
(Park Decl. ¶ 55.)
For example, the common specification describes
13
hydroxypropylmethylcellulose (HPMC) as a release controlling coating material, a pore former, a
material in an overcoat, an enhancing agent, and a binder. (’580 patent, 7:9, 7:57, 8:10, 9:34,
10:22.) These descriptions in the specification show that the patentees recognized that excipients
can have different functions depending on where and how they are incorporated into the
formulation, and that an excipient is only a “coating material” when it is in a coating. Moreover,
Plaintiff’s proposed construction broadens the scope of the claims to the point of reading out the
word “coating” from the claim term, and this runs counter to Federal Circuit precedent which
requires courts to give full “effect” and “respect” to every word in a claim term. Pause Tech LLC
v. Tivo Inc., 419 F.3d 1326, 1334 (Fed. Cir. 2005); Bicon, 441 F.3d at 950. For these reasons, this
Court declines to adopt the “and is capable of forming a coating” language.
Neither construction proposed by the parties defines the word “material.” Instead, the
proposed constructions use the word “material” as the part of the proposed definition of “coating
material.” For this reason, and because this Court declines to construe “coating” for the reasons
discussed above, this Court declines to construe “coating material” and gives it its plain and
ordinary meaning, e.g., a material used as a covering.
E. “a maximum steady state plasma concentration (Cmax) of topiramate”
Plaintiff’s Proposed
Construction
a maximum plasma
concentration (Cmax) of
topiramate reached during a
dosing interval while at
steady state
Defendants’ Proposed
Construction
a maximum plasma drug
concentration (Cmax) of
topiramate that is the
calculated mean value based
on values obtained from a
group of subjects tested
during a dosing interval while
at steady state
14
Court’s Construction
a maximum plasma
concentration (Cmax) of
topiramate reached during a
dosing interval while at
steady state that is the
calculated mean value based
on values obtained from a
group of subjects tested
Plaintiff and Defendants disagree on the meaning of “a maximum steady state plasma
concentration (Cmax) of topiramate” as used in claim 10 of the ’580 patent, claim 11 of the ’248
patent, claim 2 of the ’191 patent, and claim 11 of the ’989 patent.
The parties agree that pharmacokinetic results from clinical studies involve a mean value
that is calculated “based on values obtained from a group of subjects” that are tested. (Defs.’ Op.
Br. 20, Pl.’s Resp. Br. 23.) In other words, to determine pharmacokinetic parameters, it is
understood that at some point subjects must be tested to determine concentrations of drug in the
blood. This is supported by the specification: “unless otherwise indicated, when a drug plasma
concentration is listed, the value listed is the calculated mean value based on values obtained from
a group[] of subjects tested.” (’580 patent, 4:22-29.) Because both sides agree that the language
is factually correct, and because the language is included expressly in the patent specification, this
Court includes “calculated mean value based on values obtained from a group of subjects tested”
as part of the construction of “a maximum steady state plasma concentration (Cmax) of
topiramate.”
The parties also agree that the “maximum plasma concentration (Cmax) of topiramate”
should be based on “a dosing interval while at steady state,” a construction that is consistent with
the intrinsic evidence. However, the parties dispute whether the Cmax must be determined by
testing subjects during the dosing interval at steady state. This limitation would require the
administration of repeated doses to subjects (until steady state is reached) before measuring plasma
concentrations. This limitation would exclude steady state Cmax values that are calculated by
applying the superposition principle to data obtained from a single-dose study, a method that is
disclosed in Example 6 of the specification. (’580 patent, 18:55-19:50; see Thakker Decl. ¶¶ 37,
42, 54.) Extrinsic evidence shows that a POSA would have known that the superposition principle
15
was commonly used to obtain steady state pharmacokinetic results based on single-dose study
data. (Thakker Decl. ¶¶ 37, 58.)
This Court will not construe the claims to exclude an alternative means of accomplishing
the claimed result when the alternative means is disclosed in the specification. See 3M Innovative
Props. Co. v. Tredegar Corp., 725 F.3d 1315, 1331 (Fed. Cir. 2013). Such a construction would
require a limitation that the specification does not require. See Renishaw, 158 F.3d at 1249. For
these reasons, this Court construes “a maximum steady state plasma concentration (Cmax) of
topiramate” to mean “a maximum plasma concentration (Cmax) of topiramate reached during a
dosing interval while at steady state that is the calculated mean value based on values obtained
from a group of subjects tested.”
F. “a relative steady state AUC”
Plaintiff’s Proposed
Construction
an area under the plasma
concentration-time curve
(AUC) of topiramate from the
formulation administered
once-daily while at steady
state in relation to the AUC
of topiramate from an
immediate release
formulation administered
daily in two divided doses
while at steady state
Defendants’ Proposed
Construction
an area under the plasma
concentration-time curve
(AUC) of topiramate from the
formulation administered
once-daily while at steady
state in relation to the AUC
of topiramate from an
immediate release
formulation administered
twice a day in two equal
doses while at steady state
based on values obtained
from a group of subjects
tested by a crossover study
Court’s Construction
an area under the plasma
concentration-time curve
(AUC) of topiramate from the
formulation administered
once-daily while at steady
state in relation to the AUC
of topiramate from an
immediate release
formulation administered
daily in two divided doses
while at steady state
Plaintiff and Defendants disagree on the meaning of “a relative steady state AUC” as used
in claim 11 of the ’580 patent, claim 12 of the ’248 patent, claim 5 of the ’191 patent, and claim
12 of the ’989 patent. Both sides’ proposed constructions recite “an area under the plasma
16
concentration-time curve (AUC) of topiramate from the formulation administered once-daily
while at steady state in relation to the AUC of topiramate from an immediate release formulation.”
Such language is consistent with the intrinsic evidence, (’580 patent, 4:34-36), and this Court
adopts it.
Although the parties’ competing constructions both provide for two doses a day, the parties
disagree whether the doses should be “equal” or “divided.” The intrinsic evidence uses “divided
doses” to describe the relative steady state AUC. Moreover, Plaintiff’s expert explains that “if
only 50 mg tablets of an immediate release product are available and 25 mg of the immediate
release product is to be administered twice a day (“BID”), a POSA would know to physically
divide the 50 mg tablet into two halves. In such circumstances, the two divided doses (i.e. each
half of the tablet) would have a similar dosage amount, but they likely would not be exactly equal.”
(Thakker Resp. Decl. ¶ 44.) This Court adopts Plaintiff’s “daily in two divided doses” language.
The parties also dispute whether the specification requires the use of a crossover study to
calculate the relative steady state AUC. This limitation is not required by the claim language or
specification, and would exclude other methods for comparing formulations, such as parallel study
designs, in which the formulations are administered to different subjects. A POSA would know
that other study designs, such as parallel studies, can be used and that such studies may even be
preferable for drugs such as topiramate with relatively long half-lives. (Thakker Resp. Decl. ¶¶
35-36.) And although the specification recognizes that there is interpatient variability in blood
plasma concentrations, the specification expressly teaches that mean values, not crossover studies,
are to be used to account for the problem. (’580 patent 4:22-29.)
Moreover, the use of a crossover study in Example 6 of the specification is not sufficient
to read the limitation into the claims. “[I]t is improper to read limitations from a preferred
17
embodiment described in the specification—even if it is the only embodiment—into the claims
absent a clear indication in the intrinsic record that the patentee intended the claims to be so limited.
Liebel-Flarsheim Co., 358 F.3d at 913. The specification here does not indicate that the claim
language should be so limited; nor does it require—or even state a preference for—a crossover
study over any other kind of clinical study that could be used. (Thakker Resp. Decl. ¶¶ 33-34.)
This Court will not construe the claims to require a limitation that the specification does not
require. See Renishaw, 158 F.3d at 1249. For these reasons, this Court adopts Plaintiff’s proposed
construction.
G. “the same amount of topiramate administered as an immediate release
formulation BID”
Plaintiff’s Proposed
Construction
the equivalent amount of
topiramate administered daily
as an immediate release
formulation given twice a day
Defendants’ Proposed
Construction
the equivalent amount of
topiramate administered daily
as an immediate release
formulation given twice a day
in the same subjects
Court’s Construction
the equivalent amount of
topiramate administered daily
as an immediate release
formulation given twice a day
Plaintiff and Defendants disagree on the meaning of “the same amount of topiramate
administered as an immediate release formulation BID” as used in claims 10 and 11 of the ’580
patent, claims 11 and 12 of the ’248 patent, claims 2-6 and 14 of the ’191 patent, and claims 11
and 12 of the ’989 patent. The parties agree on the language “the equivalent amount of topiramate
administered daily as an immediate release formulation given twice a day,” and this portion of the
proposed constructions is supported by the intrinsic evidence.
The parties dispute whether the formulation must be given twice a day “in the same
subjects.” This limitation is not required by the claim language or specification, and would require
the use of crossover studies and exclude other methods for comparing formulations, such as
parallel study designs, in which the formulations are administered to different subjects. Moreover,
18
the plain language of the claim term concerns the amount of topiramate to be administered, and
Defendants provide no explanation as to why a POSA would assume that the amount of a drug to
be administered would limit the subjects who should receive the drug. For these reasons, and for
the reasons discussed above in Part IV.F, this Court finds that the formulation need not be given
twice a day “in the same subjects.”
CONCLUSION
For the reasons stated above, this Court orders that the disputed claims in the patents in suit
be construed as set forth in this Opinion. A summary of this Court’s construction of the disputed
claims is provided in the corresponding Order.
s/ Susan D. Wigenton
Susan D. Wigenton, U.S.D.J.
Orig: Clerk
cc:
Leda Dunn Wettre, U.S.M.J.
Parties
19
Claim Term
at least two different
extended release
topiramate-containing
components
population[s] of beads
release controlling
coating
coating material
Plaintiff’s Proposed
Construction
at least two extended
release topiramatecontaining components,
wherein each
component has its own
in vitro rate of drug
release
population[s] of
particles, spheres,
beads, granules, pellets,
particulates or any
structural units that
may be incorporated
into an oral dosage
form
Construction of
“population” is not
necessary. The term
has its plain and
ordinary meaning, e.g.,
group, collection, or
class.
a coating that modifies
and controls the release
of the active ingredient
Construction of
“coating” is not
necessary. The term
has its plain and
ordinary meaning, e.g.,
a covering.
a material that modifies
and controls the release
of the active ingredient
and is capable of
forming a coating
Defendants’ Proposed
Construction
at least two different
extended release
topiramate-containing
components having
different compositions
and release rates for
topiramate, within
normal variation
multiple structural units
with the same
composition and rate of
release, within normal
variation
a layer of material
coated onto a core or
other layer that
modifies and controls
the extended release of
the active ingredient
a material coated onto a
core or other layer
Construction of
“coating” is not
necessary. The term
has its plain and
ordinary meaning, e.g.,
a covering.
20
Court’s Construction
at least two extended
release topiramatecontaining components
having different in vitro
release rates for
topiramate
population[s] of
particles, spheres,
beads, granules, pellets,
particulates or any
structural units that
may be incorporated
into an oral dosage
form
Construction of
“population” is not
necessary. The term
has its plain and
ordinary meaning, e.g.,
group, collection, or
class.
a coating that modifies
and controls the release
of the active ingredient
Construction of
“coating” is not
necessary. The term
has its plain and
ordinary meaning, e.g.,
a covering.
Construction of
“coating material” is
not necessary. The term
has its plain and
ordinary meaning, e.g.,
a material used as a
covering.
Claim Term
Plaintiff’s Proposed
Construction
a maximum plasma
concentration (Cmax)
of topiramate reached
during a dosing interval
while at steady state
Defendants’ Proposed
Construction
a maximum plasma
drug concentration
(Cmax) of topiramate
that is the calculated
mean value based on
values obtained from a
group of subjects tested
during a dosing interval
while at steady state
Court’s Construction
a relative steady state
AUC
an area under the
plasma concentrationtime curve (AUC) of
topiramate from the
formulation
administered once-daily
while at steady state in
relation to the AUC of
topiramate from an
immediate release
formulation
administered daily in
two divided doses
while at steady state
an area under the
plasma concentrationtime curve (AUC) of
topiramate from the
formulation
administered once-daily
while at steady state in
relation to the AUC of
topiramate from an
immediate release
formulation
administered daily in
two divided doses
while at steady state
the same amount of
topiramate
administered as an
immediate release
formulation BID
the equivalent amount
of topiramate
administered daily as
an immediate release
formulation given twice
a day
an area under the
plasma concentrationtime curve (AUC) of
topiramate from the
formulation
administered once-daily
while at steady state in
relation to the AUC of
topiramate from an
immediate release
formulation
administered twice a
day in two equal doses
while at steady state
based on values
obtained from a group
of subjects tested by a
crossover study
the equivalent amount
of topiramate
administered daily as
an immediate release
formulation given twice
a day in the same
subjects
a maximum steady
state plasma
concentration (Cmax)
of topiramate
21
a maximum plasma
concentration (Cmax)
of topiramate reached
during a dosing interval
while at steady state
that is the calculated
mean value based on
values obtained from a
group of subjects tested
the equivalent amount
of topiramate
administered daily as
an immediate release
formulation given twice
a day
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