Sandoz Inc.v.EKR Therapeutics, LLC

Patent Trial and Appeal Board

Apr 24, 2015

11788076 (P.T.A.B. Apr. 24, 2015)

Trials@uspto.gov Paper No. 20
571-272-7822 Entered: April 24, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

SANDOZ INC.,
Petitioner,

v.

EKR THERAPEUTICS, LLC,
Patent Owner.
____________

Case IPR2015-00006
Patent 7,612,102 B2
____________

Before JACQUELINE WRIGHT BONILLA, SHERIDAN K. SNEDDEN,
and ZHENYU YANG, Administrative Patent Judges.

YANG, Administrative Patent Judge.

DECISION
Denying Institution of Inter Partes Review
37 C.F.R. § 42.108

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INTRODUCTION
Sandoz Inc. (“Petitioner”) filed a Petition for an inter partes review of
claims 1–15 of U.S. Patent No. 7,612,102 B2 (Ex. 1001, “the ’102 patent”).
Paper 1 (“Pet.”). EKR Therapeutics, LLC (“Patent Owner”) filed a
Preliminary Response. Paper 8 (“Prelim. Resp.”). We have jurisdiction
under 35 U.S.C. § 314.
For the reasons provided below, we determine Petitioner has not
established a reasonable likelihood that it would prevail in showing the
unpatentability of at least one challenged claim. Therefore, we deny the
Petition for an inter partes review.

Related Proceedings
According to the parties, Patent Owner previously asserted the ’102
patent against Petitioner in Chiesi USA, Inc., et al. v. Sandoz Inc. et al., Case
No. 1:13-cv-5723 (D.N.J.). Pet. 3; Paper 4, 1.
Petitioner concurrently filed Petitions for inter partes review of claims
in several other patents owned by Patent Owner, including IPR2015-00005
(US 8,455,524 B2), IPR2015-00007 (US 7,659,290 B2), and IPR2015-
00008 (US 7,659,291 B2).

The ’102 Patent
The ’102 patent relates to “ready-to-use premixed pharmaceutical
compositions of nicardipine or a pharmaceutically acceptable salt and
methods for use in treating cardiovascular and cerebrovascular conditions.”
Ex. 1001, Abstract. According to the ’102 patent, before its invention,
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nicardipine hydrochloride was sold in capsule form and in an injectable
intravenous form. Id. at 1:19–20. The injectable intravenous form,
CARDENE® I.V., marketed in glass ampuls in a concentration of
2.5 mg/mL, must be diluted in a compatible intravenous fluid before
administration. Id. at 1:23–30.
The requirement for diluting CARDENE® I.V. before use is
associated with a number of disadvantages, the most significant of which is
that the diluted solution is only stable for 24 hours at room temperature. Id.
at 1:39–42. Other disadvantages include variable pH levels, potential for
contamination, dosage errors, and safety hazards associated with the use of
glass ampuls. Id. at 1:42–50. The ’102 patent describes its invention as
overcoming these disadvantages. Id. at 1:51–57.

Illustrative Claims
Claims 1 and 5–7 are independent claims. Claims 1 and 6 are
representative. They read as follows:
1. A pharmaceutical composition for parenteral
administration comprising a pre-mixed aqueous solution with a
pH from about 3.6 to about 4.7 comprising:
from about 0.1 to 0.4 mg/mL nicardipine hydrochloride;
a tonicity agent selected from (i) about 4.5% to about 5%
dextrose or (ii) about 0.8% to about 0.9% sodium
chloride; and
a buffer in an amount to maintain pH from about 3.6 to
about 4.7;
the aqueous solution contained in a pharmaceutically
acceptable container such that the solution does not come
into contact with polar polymers;
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the aqueous solution when stored in the container for at least
one year at room temperature exhibiting (i) less than a
10% decrease in the concentration of nicardipine
hydrochloride and (ii) a total impurity formation of less
than about 3%.
6. A pharmaceutical composition for parenteral
administration comprising a pre-mixed aqueous solution
comprising:
from about 0.1 to about 0.2 mg/mL nicardipine
hydrochloride;
a tonicity agent selected from (i) about 46 to about 50
mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL
sodium chloride;
from 0 mg/mL to about 4 mg/mL sorbitol; and
a buffer in an amount to maintain pH from about 3.6 to
about 4.7;
the aqueous solution contained in a pharmaceutically
acceptable container comprising copolyester,
polyethylene or polyolefin;
the aqueous solution when stored in the container for at least
one year at room temperature exhibiting (i) less than a
10% decrease in the concentration of nicardipine
hydrochloride and (ii) a total impurity formation of less
than about 3%.
Claim 5 is similar to claim 1, except the concentration of
nicardipine hydrochloride is “from about 0.1 to about 0.2 mg/mL;”
and the concentration of the tonicity agents is described using mg/mL,
instead of percentage—“a tonicity agent selected from (i) about 46 to
about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium
chloride.”
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Claim 7 is similar to claim 6, except claim 7 does not include
the stability limitations (i.e., less than a 10% concentration decrease
and less than about 3% total impurity formation) recited in claim 6.

Asserted Grounds of Unpatentability
Petitioner asserts the following grounds, each of which challenges the
patentability of claims 1–15:
Basis References
§ 103 Cardene PDR1 and JP ’3642
§ 103 Cardene PDR, JP ’364, Baaske,3 and the ’405 patent4
The earliest asserted priority date of the challenged claims is April 18,
2006. Ex. 1001, 1:7–10. Thus, each asserted reference qualifies as prior art
under 35 U.S.C. § 102(b).
In support of its patentability challenge, Petitioner relies on the
Declaration of Dr. Alpaslan Yaman (Ex. 1002).

1 Cardene® I.V., Physicians’ Desk Reference, 2004 WL 2459623
(Ex. 1005, “Cardene PDR”).
2 Kenichi et al., Japanese Patent Publication JP 2002-177364, published on
June 25, 2002 (Ex. 1004, “JP ’364”)
3 Baaske et al., Stability of nicardipine hydrochloride in intravenous
solutions, Am. J. Health Syst. Pharm. 53: 1701–05 (1996) (Ex. 1006,
“Baaske”).
4 McFarlane et al., U.S. Patent No. 5,164,405, issued November 17, 1992
(Ex. 1003, “’405 patent”).
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ANALYSIS
Claim Construction
In an inter partes review, the Board interprets a claim term in an
unexpired patent according to its broadest reasonable construction in light of
the specification of the patent in which it appears. 37 C.F.R. § 42.100(b); In
re Cuozzo Speed Techs., LLC, 778 F.3d 1271, 1279–81 (Fed. Cir. 2015).
Under that standard, absent any special definitions, we assign claim terms
their ordinary and customary meaning, as would be understood by one of
ordinary skill in the art at the time of the invention, in the context of the
entire patent disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257
(Fed. Cir. 2007).
The parties dispute the construction of the term “a pre-mixed aqueous
solution,” as recited in each independent, challenged claim. See Pet. 6–7;
Prelim. Resp. 20–24. Petitioner proposes that we construe the term to mean
“an aqueous solution that is mixed and ready to use prior to its point-of-care
administration.” Pet. 6–7. Under this construction, according to Petitioner,
“formulations prepared by pharmacists hours before administration” would
fall within the scope of “a pre-mixed aqueous solution.” Id. at 7. Petitioner
points to the Specification where it states
[T]he term “pre-mixed,” as used herein, means a
pharmaceutical composition that is already mixed from the
point of manufacture and does not require dilution or further
processing before administration. The term “pre-mixed” may
also mean a pharmaceutical composition wherein the liquid
solution and the active pharmaceutical ingredient are separated
from the point of manufacture and in storage, such as when the
solution is stored in an intravenous bag and the active
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pharmaceutical ingredient is lyophilized and stored in a vial that
is connected to the bag, but not in fluid contact with the
solution until just before administration to a patient.
Ex. 1001, 11:25–36; Pet. 7. Petitioner emphasizes the second sentence in
the passage above as proof that “a pre-mixed aqueous solution” does not
have to be mixed at the point of manufacture. Pet. 7.
Patent Owner counters that the term should be construed to mean “a
ready-to-use pharmaceutical composition that is an aqueous solution already
mixed from the point of manufacture and is stable, allows medical personnel
to use prepared containers containing an injectable formulation off the shelf
without additional preparation, avoids potential contamination problems, and
eliminates dosage errors.” Prelim. Resp. 20. Patent Owner asserts that the
passage relied on by Petitioner describes two different products. Prelim.
Resp. 21. According to Patent Owner, while the first sentence refers to the
claimed “pre-mixed aqueous solution,” the second sentence “describes a
separate, alternative composition not claimed” and should not be the basis
for our claim construction. Id. at 21–22. Patent Owner’s argument is more
persuasive.
Immediately following the language Petitioner relies on, the
Specification continues: “the pharmaceutical compositions are aqueous
solutions that are administered by injection. Alternatively, the
pharmaceutical compositions may be lyophilized and then reconstituted in
isotonic saline, for example, before intravenous administration.” Ex. 1001,
11:36–40 (emphases added). When read in context, only the aqueous
solutions refer to the claimed “pre-mixed aqueous solution.” The
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lyophilized compositions cannot be aqueous. Nor can it be “pre-mixed” as it
requires reconstitution. Indeed, the ’102 patent expressly defines the term
“pre-mixed:”
As used herein, the term “pre-mixed” refers to a pharmaceutical
composition that does not require reconstitution or dilution
before administration to a patient. In contrast to ampul
formulations comprising nicardipine hydrochloride that must be
diluted prior to use in a diluent and container selected by
hospital personnel, the premixed pharmaceutical compositions
provided herein are stable at room temperature for 6 months or
longer due to the inclusion of a buffer capable of maintaining
the pH within an optimal pH range, which is typically between
3.6 to about 4.7.
Id. at 3:10–19 (emphases added).
Stability of the pre-mixed aqueous solution is the hallmark of the ’102
patent invention. It is undisputed that the diluted CARDENE® I.V. is only
stable for 24 hours at room temperature. Id. at 1:40–42; Ex. 1006, 10. The
goal of the ’102 patent is to develop stable,5 ready-to-use aqueous solutions
to overcome this disadvantage. Ex. 1001, 1:51–53; see also id. at 3:23–24
(disclosing the “production of stable, ready-to-use, premixed pharmaceutical
compositions”); id. at 3:39–40 (stating the same). The ’102 patent
summarizes the invention as “ready-to-use, premixed pharmaceutical
compositions [that] are stable at room temperature for at least one year.” Id.
at 1:61–67; see also id. at 3:46–49 (stating that the pre-mixed solutions “are
stable when maintained at room temperature for at least 6 months, at least 12

5 The Specification defines “stable” to mean “remaining in a state or
condition that is suitable for administration to a patient.” Ex. 1001, 3:51–53.
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months, at least 18 months, and at least 24 months”). According to the
Specification, “the development of a stable, ready-to-use premixed
pharmaceutical composition requires simultaneous optimization of pH and
nicardipine hydrochloride concentration, as well as selection of a
pharmaceutically compatible container.” Id. at 3:39–43.
These disclosures support Patent Owner’s contention that the
Specification “unequivocally distinguishes” the claimed pre-mixed
compositions from the point-of-care dosage forms. See Prelim. Resp. 21.
We, therefore, determine that the broadest reasonable interpretation of “a
pre-mixed aqueous solution,” consistent with the Specification, is “a ready-
to-use aqueous solution that is already mixed from the point of manufacture
and is stable at room temperature for 6 months or longer.”
Petitioner also asks us to construe “a total impurity formation,” as
recited in each independent, challenged claim. Petitioner proposes, and
Patent Owner does not object, that we construe this term to mean “a total
nicardipine-related impurity formation.” Pet. 8–9. For purposes of this
Decision, we adopt Petitioner’s construction.

Real Party in Interest
Patent Owner urges that we deny the Petition because Petitioner fails
to identify Sandoz AG and ACS Dobfar Info S.A. (“Dobfar”) as real parties
in interest with respect to the Petition. Prelim. Resp. 6–16. With the panel’s
authorization, Petitioner filed a Reply (Paper 13), and Patent Owner filed a
Sur-reply (Paper 17), addressing this issue.
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Because we deny the Petition as Petitioner has not established a
reasonable likelihood that it would prevail in showing the unpatentability of
at least one challenged claim, we need not reach the real-party-in-interest
issue.

Patentability Analysis
Prior Art Teachings
Cardene PDR teaches that CARDENE® I.V., available for
intravenous administration, is indicated for the short-term treatment of
hypertension when oral therapy is not feasible or not desirable. Ex. 1005, 4.
Each ampul contains 25 mg nicardipine hydrochloride in 10 mL solution
(i.e., at a concentration of 2.5 mg/mL) and should be diluted with 240 mL of
compatible intravenous fluid before infusion, resulting in a solution at a
concentration of 0.1 mg/mL. Id. at 1, 9.
JP ’364 teaches “a prefilled syringe having little adsorption of a drug.”
Ex. 1004, 2. Such a syringe is filled with a drug liquid or an injection liquid
before transporting. Id. at 3. According to JP ’364,
A prefilled syringe has many advantages, such as being very
simple to operate, allowing correct dosing without dose error
because the drug liquid and dose have already been set, and
avoiding bacterial infection because the drug does not need to
be prepared, even in an emergency.
Id. JP ’364 specifically teaches nicardipine hydrochloride as a
pharmacologically effective substance in the liquid. Id. at 3, 4.
The ’405 patent teaches “a stable pharmaceutical composition
containing nicardipine hydrochloride, a non-chloride isotonicity agent, a
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buffering agent and a pharmaceutically acceptable aqueous vehicle for
parenteral administration.” Ex. 1003, Abstract. According to the ’405
patent, controlling the pH level of the formulation is essential to maintain the
aqueous solubility of the nicardipine salts. Id. at 4:26–30. Specifically, the
’405 patent teaches using citrate buffer to maintain “the pH of the
composition in the range of about 3.5–4.5.” Id. at 4:42–46. In addition, the
’405 patent teaches that solutions containing either 1 mg/mL or 2.5 mg/mL
nicardipine hydrochloride showed “substantially identical” and “excellent
stability for up to 3 years at 25°C., with no significant loss in potency.” Id.
at 7:11–17, 7:28–31, Table 7.
Baaske teaches that solutions containing nicardipine hydrochloride at
concentrations of 0.05 mg/mL and 0.5 mg/mL are stable in glass containers
for up to seven days. Ex. 1006, 1, 3. In contrast, according to Baaske,
“[c]oncentrations of nicardipine hydrochloride slowly decreased in PVC
containers, sometimes to less than 85% of the initial drug concentration
within 24 hours.” Id. at 3.

Obviousness over Cardene PDR and JP ’364
Petitioner asserts that claims 1–15 would have been obvious over the
combination of Cardene PDR and JP ’364. Pet. 12–31. We determine that
Petitioner has not established a reasonable likelihood it would prevail on this
basis.
pH Levels
All challenged claims recite, either directly or through their
dependency, a nicardipine solution with “a buffer in an amount to maintain
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pH from about 3.6 to about 4.7.” Petitioner, relying on Dr. Yaman’s
Declaration, argues that
A POSA [person of ordinary skill in the art] would have
recognized that the dilution of concentrated Cardene® I.V.
having a pH of 3.5 in accordance with the Cardene PDR
instructions provides buffered solutions with a pH falling
within the range of, or a pH at least significantly overlapping
with, “about 3.6 to about 4.7.” A POSA making a pre-mixed
0.1 mg/mL nicardipine solution would have been motivated by
the Cardene PDR to choose a solution containing a buffer, and
to select such a pH range in a pre-mixed nicardipine 0.1 mg/mL
solution. Further optimization of the pH to maintain the
solubility and stability of parenteral formulations would have
been a routine step for a POSA.
Pet. 18–19 (internal citations omitted); Ex. 1002 ¶¶ 137–41. We are not
persuaded.
Cardene PDR teaches that the commercially available, concentrated
nicardipine hydrochloride (2.5 mg/mL) has a pH of 3.5. Ex. 1005, 1.
Neither party contends that Cardene PDR expressly discloses the pH of a
diluted solution having 0.1 to 0.4 mg/mL nicardipine hydrochloride. Citing
Dr. Yaman’s testimony, Petitioner argues that diluting the concentrated
nicardipine hydrochloride of Cardene PDR would “provide[] buffered
solutions with a pH falling within the range of, or a pH at least significantly
overlapping with, ‘about 3.6 to about 4.7.’” Pet. 18 (citing Ex. 1002 ¶¶ 137–
41). As noted by Patent Owner, however, evidence of record indicates that
diluting a concentrated nicardipine hydrochloride can yield pH levels outside
the claimed range of “about 3.6 to about 4.7.” Prelim. Resp. 29. For
example, Patent Owner refers to Baaske for teaching that the pH levels of
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diluted nicardipine hydrochloride can be as high as 5.9, notably higher than
4.7, the highest pH in the recited pH range. Id. (citing Ex. 1006, 3). Such
evidence on the pH levels does not support Dr. Yaman’s opinion. The
Petition and evidence cited therein do not establish sufficiently that Cardene
PDR teaches, expressly or inherently (i.e., as necessarily present or a natural
result of dilution), a composition comprising from about 0.1 to 0.4 (or 0.2)
mg/mL nicardipine and a buffer in an amount to maintain a pH from about
3.6 to about 4.7, as required in the challenged claims.
In addition, Petitioner does not rely on JP ’364 to support its argument
regarding the pH levels. In fact, as Patent Owner points out, JP ’364 does
not discuss the pH of any nicardipine solutions. Prelim. Resp. 30. Thus, we
are not persuaded that a skilled artisan, knowing the teachings of Cardene
PDR and JP ’364, would have been motivated to select the pH range for a
pre-mixed nicardipine solution as claimed.
Stability Related Limitations
All challenged claims recite “a pre-mixed aqueous solution”
comprising nicardipine hydrochloride and certain other ingredients. As
explained above, consistent with the Specification, we construe the term to
mean “a ready-to-use aqueous solution that is already mixed from the point
of manufacture and is stable at room temperature for 6 months or longer.”
See supra at 9. Petitioner’s proposed claim construction of this term does
not include the requirement of stability. See Pet. 6–7. Nevertheless, in
discussing whether the prior art taught “a pre-mixed aqueous solution,”
Petitioner mentions JP ’364 shows that nicardipine hydrochloride solutions
stored in the containers of JP ’364 “would maintain their stability over
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time.” Id. at 16. Petitioner also argues that the stability and purity
limitations are inherent properties and thus, would have been met by merely
following the teachings of Cardene PDR and JP ’364. Id. at 24–25. We are
not persuaded.
“[I]nherency may supply a missing claim limitation in an obviousness
analysis.” PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1194–95
(Fed. Cir. 2014) (citations omitted). The Federal Circuit has cautioned,
however, that the use of inherency doctrine “must be carefully circumscribed
in the context of obviousness.” Id. at 1195. Inherency “may not be
established by probabilities or possibilities.” Bettcher Indus., Inc. v. Bunzl
USA, Inc., 661 F.3d 629, 639 (Fed. Cir. 2011) (citing In re Oelrich, 666 F.2d
578, 581 (CCPA 1981)). Instead, “the limitation at issue necessarily must be
present, or the natural result of the combination of elements explicitly
disclosed by the prior art.” PAR Pharm., 773 F.3d at 1196.
For purposes of this Decision, we assume, without deciding, that one
of ordinary skill in the art would have had a reason to combine the teachings
of the prior art. Even so, it still “matters greatly whether anything the skilled
artisan would be prompted by the prior art to do is in fact within the scope of
the . . . claim.” In re Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). Thus,
Petitioner must present sufficient evidence, either from the prior art or
through its own testing data, to show that, when stored in a container taught
by JP ’364, nicardipine hydrochloride solutions prepared as suggested in the
prior art, in fact, would be “stable at room temperature for 6 months or
longer,” as “a pre-mixed aqueous solution” would require. This, Petitioner
has failed to do.
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As Patent Owner correctly points out, Cardene PDR states that the
diluted nicardipine hydrochloride solution is stable only for 24 hours at room
temperature. See Prelim. Resp. 30; Ex. 1005, 10. JP ’364 teaches the
maintenance ratio of nicardipine hydrochloride solution, after six months at
40 °C, is 95%. Ex. 1004, 8. It, however, does not disclose the concentration
of the nicardipine hydrochloride solution tested. Instead, it only identifies
the solution as “Perdipine Injection, made by Yamanouchi Pharmaceutical
Co., Ltd.” Id. Dr. Yaman acknowledges this deficiency but speculates that
it is “likely one of the concentrations used to administer the drug.” Ex. 1002
¶ 76. This statement, unsupported by persuasive evidence, is mere
conjecture. But even if we were to agree with Dr. Yaman on this point,
Dr. Yaman does not explain what the “likely” concentrations are. And even
if we were to accept that the concentrations of the nicardipine hydrochloride
solutions tested are within the ranges recited in the challenged claims, JP
’364 does not disclose, and Dr. Yaman and Petitioner do not explain, the
compositions of those nicardipine hydrochloride solutions.
Indeed, the challenged claims recite the “pre-mixed aqueous solution”
as comprising not only nicardipine hydrochloride, but also other
components, including a tonicity agent such as dextrose or sodium chloride.
Neither Dr. Yaman nor Petitioner points to the prior art to show that
nicardipine hydrochloride solutions, within the recited concentration range
and with the additional ingredients, when stored in a container taught by JP
’364, would be, in fact, “stable at room temperature for 6 months or longer.”
Nor does Petitioner provide any independent testing data to support its
inherency theory on the 6-month stability limitation. Thus, we are not
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persuaded that this limitation is necessarily present in, or is the natural result
of, the combined teachings of Cardene PDR and JP ’364.
Moreover, claims 1–6 and 12–14 recite, either directly or through
their dependency, an impurity-formation limitation, requiring the nicardipine
solution “when stored in the container for at least one year at room
temperature exhibiting . . . (ii) a total impurity formation of less than about
3%.” In addition, claim 9 recites a similar limitation over a period of three
months and claim 11 recites a similar limitation over a period of one year.
Petitioner argues that “[t]otal impurity formation over time is an inherent
property of the nicardipine hydrochloride solution and the container within
which it is stored.” Pet. 24. According to Petitioner, “[b]y merely choosing
to follow the teachings of the Cardene PDR and JP ’364, a POSA would
obtain a pre-mixed nicardipine hydrochloride solution” satisfying the recited
impurity-formation limitation. Id. We are not persuaded.
Cardene PDR states that the diluted nicardipine hydrochloride
solution is stable only for 24 hours at room temperature, and JP ’364 does
not include any teaching of impurity formation. See Prelim. Resp. 30, 31.
Nor does Petitioner provide any independent testing data to support its
inherency theory on the impurity-formation limitation. Thus, we are not
persuaded that the impurity-formation limitation is necessarily present in, or
is the natural result of, the combined teachings of Cardene PDR and JP ’364.
In sum, because Petitioner fails to sufficiently account for at least the
pH levels and the stability related limitations in the challenged claims, we
conclude that Petitioner has not established a reasonable likelihood it would
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prevail in showing that claims 1–15 would have been obvious over the
combination of Cardene PDR and JP ’364.

Obviousness over Cardene PDR, JP ’364, Baaske, and the ’405 Patent
Petitioner asserts that claims 1–15 would have been obvious over the
combination of Cardene PDR, JP ’364, Baaske, and the ’405 Patent. Pet.
31–50. We determine that Petitioner has not established a reasonable
likelihood it would prevail on this basis. We conclude so because the
teachings of Baaske and the ’405 patent do not remedy the deficiency of
Cardene PDR and JP ’364 regarding the stability related limitations, as
discussed above.
According to Petitioner, it would have been obvious to, at the point to
manufacture, “prefill” the diluted nicardipine solutions taught by Baaske and
the ’405 patent in a suitable container taught by JP ’364. Pet. 36. Thus,
Petitioner contends, Baaske and the ’405 patent teach “a pre-mixed aqueous
solution.” Id. In addition, the ’405 patent teaches that “no more than 1.5%
of the nicardipine hydrochloride could have formed impurities during 12
months at room temperature.” Id. at 41 (citing Ex. 1002 ¶ 220; Ex. 1003,
6:42–60, Example IIC, Table 7). Petitioner also refers to Baaske for
teaching nicardipine solutions remain stable in glass containers. Id. (citing
Ex. 1006, 3). In view of these teachings, Petitioner concludes, “a POSA
would have reasonably expected that a nicardipine hydrochloride solution
stored in a non-polar container would have had both the stability and purity
levels claimed.” Id. (citing Ex. 1002 ¶ 205). We are not persuaded.
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As Petitioner acknowledges, the ’405 patent reports stability data for
1.0 mg/mL and 2.5 mg/mL nicardipine hydrochloride solutions, both of
which are outside of the recited concentration range. See Pet. 40–41;
Ex. 1003, 6:46–60, 7:11–17. The ’405 patent also shows data of nicardipine
hydrochloride solutions “using a 1:10 dilution.” Ex. 1003, 9:40–41. The
dilution results in a nicardipine hydrochloride solution of 0.1 mg/mL, within
the claimed concentration range. The data of the diluted nicardipine
hydrochloride solutions, however, relate to the compatibility with buffered
formula, and not stability or purity. Id. at 9:38–45. Indeed, the diluted
solutions were examined only for appearance “after mixing,” and not for any
prolonged period of time, certainly not “6 months or longer,” as required by
our construction of “a pre-mixed aqueous solution,” or one year, as further
required in claims 1–6 and 10–14. Id. at 9:46–47, Tables 9 and 10.
Similarly, the concentrations of the nicardipine hydrochloride
solutions studied in Baaske are 0.5 mg/mL and 0.05 mg/mL, both of which
are outside of the claimed concentration range. Ex. 1006, 1. In addition,
Baaske only reports that the nicardipine hydrochloride solutions are stable
for up to seven days, significantly shorter than “6 months or longer” or one
year. Id.
Petitioner, again, resorts to an inherency argument. Pet. 42. But, as
explained above, neither the prior art nor any other evidence of record
addresses adequately the stability, and specifically, the impurity formation,
of nicardipine solutions within the recited concentration and with the
additional ingredients required by the claims over “6 months or longer” or
one year, as required by our claim construction, or as recited in the
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challenged claims. For example, Petitioner does not provide any
independent testing data to support the inherency theory. Thus, we are not
persuaded that the 6-month stability requirement, and specifically the
impurity-formation limitation, are necessarily present, or is the natural result
of the combination of the teachings of Cardene PDR, JP ’364, Baaske, and
the ’405 Patent.
In sum, because Petitioner does not sufficiently explain how the
combined prior art teachings would have suggested the 6-month stability
requirement and the impurity-formation limitation, we conclude that
Petitioner has not established a reasonable likelihood it would prevail in
showing that claims 1–15 would have been obvious over the combination of
Cardene PDR, JP ’364, Baaske, and the ’405 Patent.

CONCLUSION
For the foregoing reasons, the information presented in the Petition
and accompanying evidence do not establish a reasonable likelihood that
Petitioner would prevail in showing the unpatentability of any one of claims
1–15 of the ’102 patent.

ORDER
Accordingly, it is
ORDERED that Petitioner’s request for an inter partes review of
claims 1–28 of the ’102 patent is denied.

IPR2015-00006
Patent 7,612,102 B2

20

For PETITIONER:

Matthew Kreeger
Matthew D’Amore
Elizabeth Cary Miller
David J. Austin
MORRISON & FOERSTER LLP
mkreeger@mofo.com
mdamore@mofo.com
emiller@mofo.com
daustin@mofo.com

For PATENT OWNER:

Edgar H. Haug
Nicholas F. Giove
FROMMER LAWRENCE & HAUG LLP
ehaug@flhlaw.com
ngiove@flhlaw.com