Shire LLC et al v. Sandoz Inc.

Filing 141

ORDER - Claim Construction, by Judge R. Brooke Jackson on 11/13/12. (alvsl)

IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLORADO
Honorable R. Brooke Jackson
Civil Action No. 11-cv-01110-RBJ-KMT
SHIRE LLC,
SUPERNUS PHARMACEUTICALS, INC.,
SHIRE DEVELOPMENT INC.,
SHIRE INTERNATIONAL LICENSING B.V.,
AMY F.T. ARNSTEN, PH.D.,
PASKO RAKIC, M.D., and
ROBERT D. HUNT, M.D.,
Plaintiffs,
v.
SANDOZ INC.
Defendant.

ORDER – CLAIM CONSTRUCTION

The case is before the Court on disputes concerning the meaning of five terms in a utility
patent. The briefing was completed on March 23, 2012, and the Court heard argument on
August 10, 2012.
Case History
This case involves a number of disputes arising from three utility patents involving
pharmaceuticals. Shire LLC, along with plaintiffs Supernus Pharmaceuticals, Inc., Amy F.T.
Arnsten, Ph.D., Pasko Rakic, M.D., and Robert D. Hunt, M.D., began this case on April 27,
2011, alleging that Sandoz, Inc. infringed United States Patent Nos. 5,854,290 (“the ‘290
patent”), 6,287,599 (“the ‘599 patent”), and 6,811,794 (“the ‘794 patent”). Sandoz, Inc.

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answered and counterclaimed for a declaratory judgment of non-infringement and invalidity of
the plaintiffs’ patents [#19].
Drs. Arnsten, Rakic and Hunt are the owners of the ‘290 patent, entitled “Use of
Guanfacine in the Treatment of Behavioral Disorders.” Supernus Pharmaceuticals is the owner
of the ‘599 and ‘794 patents, entitled “Sustained Release Pharmaceutical Dosage Forms with
Minimized pH Dependent Dissolution Profiles.” Shire holds an exclusive license under the ‘290,
‘599, and ‘794 patents with respect to drug products containing the active ingredient guanfacine.
Shire is also the owner of New Drug Application (“NDA”) No. 022037, which was approved by
the Food and Drug Administration (“FDA”) for the manufacture and sale of guanfacine
hydrochloride extended release tablets, what are marketed under the name “Intuniv.”
Sandoz sought approval from the FDA to engage in the commercial manufacture and sale
of the generic guanfacine hydrochloride extended release tablets before plaintiffs’ patents
expired. On March 14, 2011, pursuant to §505(j)(2)(B)(ii) of the FDCA, Sandoz sent a
notification to plaintiffs asserting the patents-in-suit are invalid, unenforceable, and/or will not be
infringed by Sandoz’s product. Following Sandoz’s Notice Letter, Plaintiffs brought this
infringement action. [#1].
On June 3, 2012 the Court granted the parties’ Joint Motion for Consolidation [#112] and
consolidated the present case with related case Shire LLC et al. v. Sandoz, Inc., Case No. 1:12cv-00040-MSK-MEH (D. Colo.) [#121]. On August 10, 2012 the Court held a Markman
Hearing on the disputed claims in the ‘599 and ‘794 patents [#129]. Prior to the hearing, the
parties jointly notified the Court that the ‘290 patent was dedicated to the public on March 22,
2012 and therefore would no longer be a subject of the current litigation.

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Conclusions
Prior to and in the course of the Markman Hearing, the parties reached agreement on the
construction of several claims identified as disputed in their claim construction briefing. The
following terms remain before the Court for construction: (1) “pH dependent agent that
increases the rate of release of said at least one pharmaceutically active agent from the tablet at a
pH in excess of 5.5;” (2) “agent that increases the solubility of said at least one pharmaceutically
active agent at a pH of greater than 5.5;” (3) “agent maintains an acidic microenvironment in the
composition;” (4) “reducing the likelihood of side effects associated with the administration of
guanfacine;” and (5) “about.”
Claim construction is a matter of law for the Court. Markman v. Westview Instruments,
Inc., 517 U.S. 370, 384-91 (1996). The objective is to give disputed terms in a patent claim the
meaning that a person of ordinary skill in the relevant art would have given them at the time of
the invention unless the patent applicant has clearly and unambiguously defined the terms
differently. See, e.g., Honeywell Int’l Inc. v. Universal Avionics Sys. Corp., 493 F.3d 1358, 1361
(Fed. Cir. 2007).
The Court principally considers “intrinsic evidence,” i.e., the words of the claim itself in
the context of the entire patent including as relevant the specification and the prosecution history.
Phillips v. AWH Corp., 415 F.3d 1303, 1313-17 (Fed. Cir. 2005), cert. denied, 546 U.S. 1170
(2006). The specification is “the single best guide to the meaning of a disputed term.” Vitrionics
Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). The court may not, however,
read limitations from the specification, particularly the disclosed embodiments, into the claim.
Phillips, 415 F. 3d at 1323-24. “Extrinsic evidence” such as dictionaries, treatises and, in some

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cases, expert testimony can also be considered, although such evidence generally should be
given less weight than intrinsic evidence. Phillips, 415 F.3d at 1317-19.
The term “pH dependent agent that increases the rate of release of said at least one
pharmaceutically active agent from the tablet at a pH in excess of 5.5.” ‘599 Patent: Claims 1-30,
‘794 Patent: Claims 3-12
The parties set forth proposed definitions in a Joint Claim Construction and Prehearing
Statement [#99]. Shire proposes the definition: “agent that increases the rate of release of the
pharmaceutically active agent from a tablet in an environment that has a pH above 5.5 relative to
an environment that has a pH of 5.5 or below.” Sandoz proposes a definition of “a substance that
increases the rate of release of a pharmaceutically active agent from a composition in
surrounding media having a pH above 5.5.”
The parties’ definitions are nearly identical aside from Shire’s proposed comparative
language. During oral argument, the parties made it clear that the crux of their disagreement is
the inclusion of the phrase “relative to an environment that has a pH of 5.5 or below.” Shire
insists that the comparison is implicit in the disputed term: i.e., the agent must be pH-dependent
and therefore behave differently at different pH levels.
Shire contends that both the plain language of the claim and the specification illustrate
that their proposed comparative language is implied. In support, Shire points to the
representation of the dissolution data represented in Table 2 of the ‘599 and ‘794 patents. That
an agent is “pH-dependent” means that the agent increases the release of the pharmaceutically
active agent more in higher pH environments than in lower pH environments. Shire argues that a
person of ordinary skill in the art would interpret the term as having to do with different things at
different pH levels. If Sandoz’s definition is adopted, Shire contends that the construction would

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allow for an increase of the rate of release at pH levels below 5.5 which would be in
contravention of the invention.
Although not binding on this Court, Shire’s proposed construction is further supported by
the claim constructions of other district courts who have construed these same patents. The
United States District Court for the District of Delaware construed an identical term to mean
“agent that is neither the non-pH dependent sustained release agent nor the pharmaceutically
active agent, and that increases the rate of release of the pharmaceutically active agent from a
tablet more in an environment that has a pH above 5.5 than in an environment that has a pH of
5.5 or below.” Shire LLC, et al v. Teva Pharmaceuticals USA Inc., et al, No. 10-329-RGA, 2012
WL 975694, at *5-6 (D. Del. March 22, 2012) (emphasis added). The United States District
Court for the Northern District of California, San Francisco Division also adopted plaintiffs’
proposed definition for the identical term. In that case the court found that “[t]he ordinary,
supported, and sufficiently definite meaning of the term is that the agent increases the rate of
release of the drug in an environment having a pH in excess of 5.5, as compared to an
environment of pH 5.5 or below.” Shire LLC, et. Al v. Impax Laboratories, Inc., et al., No. 105467 RS, 2012 WL 1980803, at *5-7 (N.D. Cal. June 1, 2012).
Sandoz, in contrast, argues that Shire’s definition improperly narrows the term. Sandoz
argues that Shire’s proposed language is unsupported by the claim language and the
specification. The proper comparison, in Sandoz’s view, is between a tablet with and without a
pH-dependent agent. Sandoz argues that their definition is supported by the intention behind the
alleged invention. The “problem” that the alleged invention is trying to solve is how to increase
the rate of release in the intestine, where there is a higher pH level. A high rate of release in the
stomach, where the pH is 1 or 2, is not an issue the invention seeks to solve.

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Although Sandoz’s definition appears at first blush to be simpler, the Court finds that it is
Shire’s definition that most closely reflects the specification and the purpose of the patent. Table
2 of the ‘599 patent compares the controls against the compositions covered by the patent above
pH 5.5 and below pH 5.5. See PD0052-22A and PD0052-25B. The Court also finds the
specification language cited by both parties supports Shire’s definition. The specification states
that “[i]t is an object of the present invention to provide a pharmaceutical composition with a
minimized pH dependent or a pH-independent dissolution profile.” ‘599 col. 1: 28-30. This goal
is achieved only by improving the rate of release in pH levels above 5.5 more than in areas
below pH 5.5. Although Sandoz would have the Court focus only on the invention’s behavior
while in the small intestine, there is intrinsic evidence that the invention is intended and designed
to be active throughout the entire gastrointestinal tract. The Court finds that the intrinsic
evidence more strongly supports that additional comparator language that Shire proposes.
Therefore, The Court adopts for the meaning of the term “pH dependent agent that
increases the rate of release of said at least one pharmaceutically active agent from the tablet at a
pH in excess of 5.5,” Shire’s proposed definition of: “agent that increases the rate of release of
the pharmaceutically active agent from a tablet in an environment that has a pH above 5.5
relative to an environment that has a pH of 5.5 or below.”
The term: “agent that increases the solubility of said at least on pharmaceutically active
agent at a pH of greater than 5.5.” Patent ‘599: Claims 4, 11, 12, 14.
For this term Shire proposes the construction “agent that increases the amount of the
pharmaceutically active agent that will dissolve in a given amount of another substance in an
environment which was a pH above 5.5 relative to an environment which has a pH of 5.5 or
below.” Sandoz’s proposed construction is as follows: “a substance that increases the amount of

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a pharmaceutically active agent that will dissolve when the surrounding media has a pH above
5.5.”
Both parties agree that their dispute here is in effect the same as for the previous disputed
term. That is, the dispute is over Shire’s proposed comparator. As the Court resolved the
previous term in favor of Shire’s proposed definition, Shire’s definition will be adopted here as
well for the reasons articulated above.
Therefore, the Court adopts the meaning for the term “agent that increases solubility of
said at least one pharmaceutically active agent at a pH of greater than 5.5” Shire’s proposed
definition of “agent that increases the amount of the pharmaceutically active agent that will
dissolve in a given amount of another substance in an environment which has a pH above 5.5
relative to an environment which has a pH of 5.5 or below.”
The term: “agent that maintains an acidic microenvironment in the composition.” Patent
‘599: Claim 13
At the hearing held on August 10, 2012 Sandoz represented to the Court that there was no
longer a dispute over this term and stipulated to Shire’s proposed definition. Therefore, the
Court adopts the following proposed construction: “agent that imparts an acidic character to the
regions immediately around or in close proximity to the pharmaceutically active agent in the
composition.”
The term: “reducing the likelihood of side effects associated with the administration of
guanfacine.” Patent ‘794: Claims 8-12.
Shire proposes the following definition: “reducing the probability of side effects resulting
from guanfacine administration.” Sandoz proposes a definition of “decreasing the incidence or

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severity of side effects compared to administering the same amount of guanfacine as an
immediate-release.”
Shire’s proposed definition is nearly identical to the language of the disputed claim.
During the Markman hearing Shire clarified that it would also accept the use of the word
“likelihood” instead of “probability,” which would make their proposed definition the same as
the disputed term. Shire, in effect, is arguing that this term is unambiguous and does not require
construction. Shire argues that the specification in the ‘794 patent lays out three possibilities for
the reduction of side effects: (1) the reduction in the number of side effects, (2) the reduction in
the likelihood of side effects, and (3) the reduction of the severity of possible side effects. Col.
3, line 48-61. Shire argues that the disputed term is simply restating the second of those three
options, and thus Sandoz’s proposed construction adds limitations that are not present in the
claim language.
Whereas Shire argued for a comparator in earlier disputed terms, Sandoz does so now.
Sandoz argues that Shire’s proposed definition provides no context. Sandoz maintains that
Shire’s definition fails to describe what the claimed reduction in side effects is compared to. The
proper comparator, as found in the specification, is “immediate release composition.” ‘794
patent: col. 11, line 61-67; Table 10. According to Sandoz, the term can only be understood by
looking to the comparison suggested in the specification.
The Court finds that the claim term is clear on its face and requires no construction or
substitution of the word “probability” for “likelihood.” Those words are not appreciably
different, and at the Markman hearing Shire stated that it could not articulate why such a
substitution was made. The example given in the specification does indeed show the claimed
invention’s reduction of side-effect with respect to an available immediate release composition.

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However, adding that limitation to a clear claim term is unnecessary and will not aid a person of
ordinary skill in the art to understand the term. The Court declines to limit the claim term
because of an example given in the specification: “claims will not be read restrictively unless the
patentee has demonstrated a clear intention to limit the claim scope using words of expression of
manifest exclusion or restriction.” Martek Biosciences Corp. v. Nutrinova, Inc., 579 F.3d 1363,
1381 (Fed. Cir. 2009).
Therefore, the Court finds that the term is clear on its face and adopts the following
definition: “reducing the likelihood of side effects associated with the administration of
guanfacine.”
The term “about.” Patent ‘599: Claims 18-23
Several claims in the ‘599 patent state that a component is “present in the composition in
an amount of from about __ wt. % to about ___ wt. %.” The parties disagree on the meaning of
the term “about.” Shire proposes that “about” should be construed to mean “approximately.”
Sandoz proposes that “about” should be construed to refer to proposed numeric ranges that
account for uncertainty based on the number of significant figures used in the numeric ranges
cited in the claims.
Shire argues that under the case law it is improper to ascribe a numerical value to the
word “about.” Shire cites to the case Modine Mfg. Co. v. U.S. Int’tl Trade Comm’n, 75 F.3d
1545, 1551 (Fed. Cir. 1995) for the proposition that “[o]rdinarily a claim element that is claimed
in general descriptive words, when a numerical range appears in the specification and in other
claims, is not limited to the numbers in the specification or other claims.”
Sandoz argues that the meaning of the term “about” is subject to interpretation, because it
does not have a universal meaning in patent claims. Sandoz correctly points out that neither the

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specification nor the prosecution history of the ‘599 patent provides a definition of the scope of
the ranges described by the “about” term. Sandoz argues that a person having ordinary skill in
the art would understand “about” to “allow for standard measuring errors by applying basic
rounding concepts based on the number of significant figures in the measurements.” [#90] at 29.
Sandoz suggests a unique range for Claims 18-23. The proposed ranges were agreed to, and
accepted by the court, in the prior case in the Northern District of California. See [#95]-1 at 1315.
Although Shire agreed to Sandoz’s proposed ranges in another action, neither party
argues that they are now bound by the prior agreement. Importantly, no other court has been
asked to construe this claim term. Sandoz is correct that nothing in the specification indicates
what numerical range is meant by “about.” It is for that reason that the Court is disinclined to
impose such a range in this instance. Neither party has pointed to any supporting reference in the
specification that supports their construction. Therefore, the Court must turn to extrinsic
evidence. See Philips, 415 F.3d at 1317. As stated above, “claims will not be read restrictively
unless the patentee has demonstrated a clear intention to limit the claim scope using words of
expression of manifest exclusion or restriction.” Martek 579 F.3d at 1381 (Fed. Cir. 2009).
Without some indication in the specification that the patentee intended a reference to a definite
numerical limitation, the Court will not impose one here. Further, the Court finds that a person
having ordinary skill in the art would understand “about” to mean an approximate, but nonspecific, numerical range.
Therefore, the Court adopts the construction “approximately” for the term “about.”

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DATED this 13th day of November, 2012.
BY THE COURT:

___________________________________
R. Brooke Jackson
United States District Judge

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