Endo Pharmaceutical Inc.v.Depomed, Inc.

Patent Trial and Appeal Board

Sep 21, 2015

09282233 (P.T.A.B. Sep. 21, 2015)

Trials@uspto.gov Paper 69
571-272-7822 Entered: September 21, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

ENDO PHARMACEUTICALS INC.,
Petitioner,

v.

DEPOMED, INC.,
Patent Owner.
____________

Case IPR2014-00654
Patent 6,340,475 B2
____________

Before ERICA A. FRANKLIN, GRACE KARAFFA OBERMANN, and
TINA E. HULSE, Administrative Patent Judges.

FRANKLIN, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
IPR2014-00654
Patent 6,340,475 B2

2
INTRODUCTION I.
Endo Pharmaceuticals Inc. (“Petitioner”) filed a Corrected Petition
requesting an inter partes review of claims 1, 2, 8–15, 43, 54, 55, 57, 58, 61,
62, and 66 of U.S. Patent No. 6,340,475 B2 (Ex. 1001, “the ’475 patent”).
Paper 5 (“Pet.”). Depomed, Inc. (“Patent Owner”) filed a Preliminary
Response to the Petition. Paper 11 (“Prelim. Resp.”). On September 29,
2014, an inter partes review of claims 1, 2, 8, 9, 13–15, 43, 57, 58, 61, 62,
and 66 was instituted. Paper 12 (“Dec. Inst.”). Patent Owner filed a
Response to the Petition. Papers 26 (confidential), 27 (public) (“PO Resp.”).
Petitioner filed a Reply to Patent Owner’s Response. Papers 41
(confidential), 42 (public) (“Pet. Reply”).
Both parties filed motions to exclude certain exhibits and testimony.
Paper 52 (Petitioner); Paper 54 (Patent Owner). Both parties opposed the
other’s motion to exclude. Paper 55 (Petitioner Opposition); Paper 57
(Patent Owner Opposition). And both parties filed reply briefs in support of
their motions to exclude. Paper 59 (Petitioner Reply); Paper 60 (Patent
Owner Reply).
Patent Owner also filed a Motion for Observation (Paper 53) on
certain cross-examination testimony of Petitioner’s declarant, Dr. Clive
Wilson, and Petitioner filed a Response (Paper 56).
A consolidated oral hearing for this proceeding and Cases IPR2014-
00652 and IPR2014-00656 was held on June 15, 2015, a transcript of which
has been entered in the record.
1
Paper 68 (“Tr.”).

1
The parties filed joint Objections to Demonstrative Exhibits. Paper 65.
Some of those objections were addressed during a conference call with the
IPR2014-00654
Patent 6,340,475 B2

3
The Board has jurisdiction under 35 U.S.C. § 6(c). In this Final
Written Decision, issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R.
§ 42.73, we determine Petitioner has not shown by a preponderance of the
evidence that challenged claims 1, 2, 8–15, 43, 54, 55, 57, 58, 61, 62, and 66
are unpatentable.
A. Related Proceedings
Petitioner and Patent Owner identify various district court actions
involving the ’475 patent, including an action involving the parties titled
Depomed, Inc. v. Endo Pharmaceuticals Inc., L.P., No. 3:13-02467
(D.N.J.). Pet. 1; Paper 8, 2–3.
The Board instituted inter partes review proceedings involving U.S.
Patent No. 6,635,280 B2 (“the ’280 patent”) (IPR2014-00656); and U.S.
Patent No. 6,723,340 (IPR2014-00652).
The Board issued Final Written Decisions in inter partes review
proceedings involving the ’280 patent (IPR2014-00377), and the ’475 patent
(IPR2014-00378 and IPR2014-00379), which were initiated by Petitioner
Purdue Pharma LP. In those Decisions, the Board found none of the
challenged claims unpatentable.
B. The ’475 Patent (Ex. 1001)
The ’475 patent relates to drugs formulated as unit oral dosage forms
by incorporating them into polymeric matrices comprising hydrophilic
polymers that swell upon imbibition of water to a size large enough to

Board. Paper 66. In this Final Written Decision, we rely directly on the
arguments presented properly in the parties’ briefs and the evidence of
record. The demonstrative exhibits were only considered to the extent they
are consistent with those arguments and evidence.
IPR2014-00654
Patent 6,340,475 B2

4
promote gastric retention of the drug during the fed mode. Ex. 1001,
Abstract. Drugs administered by conventional tablets generally become
available to body fluids at a high rate initially, followed by a rapid decline.
Id. at 1:31–33. To address this delivery pattern, controlled drug delivery
systems were introduced in the 1970s. Id. at 1:35–37. Many of the
controlled delivery systems utilize hydrophilic, polymeric matrices that
provide controlled release of sparingly soluble drugs. Id. at 1:44–46. For
soluble drugs, however, such matrices do not provide adequate control of
drug release. Id. at 1:46–50.
The claimed invention allows drugs that are highly soluble in water to
be administered orally in a way that will prolong their delivery time to
spread their release rate more evenly throughout the duration of the fed
mode. Id. at 5:32–36. That more even release rate reduces the problem of
transient overdosing, and controls the dosage to safer and more effective
levels over an extended period of time. Id. at 5:36–41. Moreover, particles
exceeding about one cm in size are larger than the pylorus and thus, retained
in the stomach for approximately four to six hours. Id. at 11:66–12:2. The
Specification states that these benefits are due to using a polymeric matrix
that is water-swellable rather than just hydrophilic, that has an erosion rate
substantially slower than its swelling rate, and that releases the drug
primarily by diffusion. Id. at 5:57–62. Preferred polymeric matrices include
water-swellable polymers such as hydroxypropylmethylcellulose (“HPMC”)
and poly(ethylene oxide) (“PEO”). Id. at 7:54–8:51.
C. Illustrative Claims
Claims 1 and 43 of the ’475 patent are independent claims.
Claims 1 and 43 are illustrative and are reproduced below:
IPR2014-00654
Patent 6,340,475 B2

5
1. A controlled-release oral drug dosage form for
releasing a drug whose solubility in water is greater than one
part by weight of said drug in ten parts by weight of water, said
dosage form comprising a solid polymeric matrix with said drug
dispersed therein at a weight ratio of drug to polymer of from
15:85 to 80:20, said polymeric matrix being one that swells upon
imbibition of water thereby attaining a size large enough to
promote retention in the stomach during said fed mode,
that releases said drug into gastric fluid by the dissolution and
diffusion of said drug out of said matrix by said gastric fluid,
that upon immersion in gastric fluid retains at least about 40% of
said drug one hour after such immersion and releases
substantially all of said drug within about eight hours after such
immersion, and that remains substantially intact until
substantially all of said drug is released.

43. A method of administering to a subject a drug that is
therapeutic to said subject when absorbed in the stomach where
said drug has at least one ionized group in the pH range 5
through 8, said method comprising orally administering to said
subject a dosage form of said drug while said subject is in a fed
mode, said dosage form comprising a solid polymeric matrix
with said drug dispersed therein at a weight ratio of drug to
polymer of from about 0.01:99.99 to about 80:20, said
polymeric matrix being one that:
(a) swells upon imbibition of gastric fluid to a size large
enough to promote retention in the stomach during
said fed mode,
(b) releases said drug into gastric fluid by the dissolving
of said drug by said gastric fluid and either erosion of
said matrix or diffusion of said dissolved drug out of
said matrix,
(c) retains at least about 40% of said drug one hour after
such immersion in gastric fluid,
(d) releases substantially all of said drug within about ten
hours after such immersion, and
IPR2014-00654
Patent 6,340,475 B2

6
(e) remains substantially intact until all of said drug is
released, thereby extending the release rate of said
drug with time during said fed mode while releasing
substantially all of said drug within said stomach
where said drug is maintained In an acidic
environment.

D. The Prior Art
Shell US 5,007,790, issued Apr. 16, 1991
(“the Shell ’790 patent”)
Ex. 1005
Edgren US 4,871,548, issued Oct. 3, 1989
(“the ’548 patent”)
Ex. 1006
Shell WO 93/18755, published Sept. 30, 1993
(“the Shell 1993 publication”)
Ex. 1007
Baveja Zero-Order Release Hydrophilic Matrix
Tablets of β-adrenergic Blockers, 39 INT’L J.
OF PHARM. 39–45 (1987).
Ex. 1008
Petitioner’s evidence includes, in part, the two Declarations of Clive
Wilson, Ph.D. Ex. 1011, 1042, and the Declaration of Kinam Park, Ph.D.,
Ex. 1019. Patent Owner’s evidence includes, in part, the Declaration of
Harold B. Hopfenberg, Ph.D., Ex. 2015.
E. The Instituted Grounds of Unpatentability
Trial was instituted for claims 1, 2, 8–15, 43, 54, 55, 57, 58, 61, 62,
and 66 of the ’475 patent on the following grounds:
A. Claims 1, 2, 8, 9, 13–15, 61, and 62, as obvious over Baveja, the ’548
patent, the Shell 1993 publication, and the Shell ’790 patent; and
B. Claims 43, 57, 58, and 66 as obvious over the Shell 1993 publication
in view of Baveja and Colombo.
IPR2014-00654
Patent 6,340,475 B2

7
ANALYSIS II.
A. Claim Construction
In an inter partes review, the Board interprets claim terms in an
unexpired patent according to the broadest reasonable construction in light
of the specification of the patent in which they appear. 37 C.F.R.
§ 42.100(b); In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1278–79 (Fed.
Cir. 2015). Under that standard, and absent any special definitions, we give
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 re
Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any special
definitions for claim terms must be set forth with reasonable clarity,
deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed.
Cir. 1994).
1. Previously Construed Terms
The parties do not contest the construction of the following claim
terms that we set forth in the Decision to Institute:
Claim Term Claim(s) Construction
“gastric fluid” 1, 43 “both the fluid in the stomach and
simulated or artificial fluids
recognized by those skilled in the art
as a suitable model for the fluid of the
human stomach” (Dec. Inst. 6)
“releases substantially
all of said drug within
about ten hours after
such immersion”
43 “at least 80% of the drug has been
released after ten hours of immersion
in gastric fluid” (Dec. Inst. 6)
IPR2014-00654
Patent 6,340,475 B2

8
Claim Term Claim(s) Construction
“substantially intact” 1, 43 “substantially retains its size and
shape without deterioration due to
becoming solubilized in the gastric
fluid or due to breakage into
fragments or small particles” (Dec.
Inst. 6–7)
PO Resp. 14; Pet. Reply 2.
Because nothing in the full record developed during trial persuades us
to deviate from our prior constructions, we continue to consider those
constructions as the broadest reasonable constructions consistent with the
Specification, and, on that basis, we adopt them for purposes of this
Decision.
2. “releases said drug . . . by the dissolution and diffusion of said drug
out of said matrix” / “releases said drug . . . by the dissolving of said drug .
. . . and either erosion of said matrix or diffusion of said dissolved drug out
of said matrix”
The term “releases said drug . . . by the dissolution and diffusion of
said drug out of said matrix” (i.e., the “dissolution and diffusion” limitation)
appears in independent claim 1. And the term “releases said drug . . . by the
dissolving of said drug . . . and either erosion of said matrix or diffusion of
said dissolved drug out of said matrix” (i.e., the “erosion or diffusion”
limitation) appears in independent claim 43. In our Decision to Institute, we
construed both terms according to their plain and ordinary meaning and
declined to import any requirement that the drug release occur “primarily”
by diffusion in claim 1, or by “rate-controlling” erosion or diffusion in claim
43. Dec. Inst. 7–8.
IPR2014-00654
Patent 6,340,475 B2

9
In its Response, Patent Owner requests that we reconsider our
construction of those terms. PO Resp. 14–15. Patent Owner proposes that
the “dissolution and diffusion” limitation means “rapid dissolution of the
drug out of the water-swollen matrix, such that the drug is released at a rate
controlled by the rate of diffusion”; and that the “erosion or diffusion”
limitation means “releases said drug into gastric fluid by either (a) rapid
dissolution of the drug followed by slow rate-controlling diffusion of the
drug out of said matrix or (b) rapid dissolution of the drug and rate-
controlling erosion of said matrix.” PO Resp. 15–16. Petitioner opposes
Patent Owner’s proposed construction, arguing that it is inconsistent with the
broadest reasonable construction standard. Pet. Reply 2.
As an initial matter, we note that we construed the “dissolution and
diffusion” limitation of the ’475 patent in the Final Written Decision entered
in IPR2014-00378. There, we determined that the broadest reasonable
interpretation of the limitation is “releases the drug by dissolution of the
drug in the matrix followed by diffusion of the drug out of the matrix.”
Purdue Pharma L.P. v. Depomed, Inc., IPR2014-00378, slip op. at 9–12
(PTAB July 8, 2015) (Paper 73). With this construction as a backdrop, we
proceed to consider Patent Owner’s arguments about its proposed alternate
construction.
Patent Owner argues that the district courts and the parties previously
agreed to its proposed constructions. PO Resp. 15. Given our different
claim construction standard, however, we are not bound by the prior district
court constructions or any alleged agreements between the parties made in
district court.
IPR2014-00654
Patent 6,340,475 B2

10
Patent Owner then argues that the claim language supports its
construction because the claim terms recite releasing the drug into gastric
fluid by a particular mechanism in the context of a controlled release dosage
form. Id. at 16–17. Specifically, Patent Owner argues that a person of
ordinary skill in the art would understand that a controlled release dosage
form is characterized by its rate-controlling drug release mechanism. Id. at
17.
Even if a person of ordinary skill in the art would understand that a
controlled release dosage form is characterized by its rate-controlling drug
release mechanism, the claim language does not require expressly a
particular rate-controlling drug release mechanism. For example, the claim
language does not recite that diffusion is the rate-controlling drug release
mechanism of claim 1. Rather, the language of claim 1 states simply that
drug is released by “dissolution and diffusion.” And, as explained by the
Banker & Rhodes reference—which Patent Owner’s declarant relies heavily
on—systems can be “dissolution rate-limited or diffusion-controlled.” Ex.
1025,
2
589; see also id. at 581–582 (describing dissolution-controlled
systems and diffusional-controlled systems); Ex. 2015 ¶ 44 (Dr. Hopfenberg
discussing the Banker & Rhodes reference). Based on the full record
developed during trial, the broadest reasonable interpretation of the
“dissolution and diffusion” term is not limited to diffusion-controlled drug
release.

2
Gwen M. Jantzen & Joseph R. Robinson, Sustained and Controlled-
Release Drug Delivery Systems, in MODERN PHARMACEUTICS 575 (Banker &
Rhodes 3d ed., 1996) (Ex. 1025, “Banker & Rhodes”).
IPR2014-00654
Patent 6,340,475 B2

11
Similarly, claim 43 simply states that drug is released “by the
dissolving of said drug by said gastric fluid and either erosion of said drug
by said gastric fluid or diffusion of said dissolved drug out of said matrix.”
Ex. 1001, claim 43. Nothing in this language dictates that the rate-
controlling mechanism of release is either by erosion or diffusion (as
opposed to, for example, dissolution).
Moreover, we are not persuaded that the Specification requires Patent
Owner’s construction. Our reviewing court has warned that, “[a]bsent claim
language carrying a narrow meaning, the PTO should only limit the claim
based on the specification or prosecution history when those sources
expressly disclaim the broader definition.” In re Bigio, 381 F.3d 1320, 1325
(Fed. Cir. 2004) (emphasis added). Here, the Specification does not
expressly disclaim any mechanism of drug release. Indeed, most of the ’475
patent claims are directed to drug dosage forms that release the drug by
erosion or diffusion (as with claim 43), reciting that the dosage form
“releases said drug into gastric fluid by the dissolving of said drug by said
gastric fluid and either erosion of said matrix or diffusion of said dissolved
drug out of said matrix.” Ex. 1001, claim 43; see also independent claims
19, 22, 24, 27, 28, 29, 30, 32, 33, 34, 37, 38, 39, 40, 42, 44 (reciting similar
“erosion or diffusion” limitations). Thus, we do not find that Patent Owner
has established persuasively that the Specification provides a basis for
narrowing the claimed “dissolution and diffusion” limitation of claim 1.
Patent Owner then argues that we have conflated the different
inventions of claim 1 and claim 43. PO Resp. 18. Patent Owner
distinguishes the claims because claim 1 is directed to highly soluble drugs,
whereas claim 43 is directed to any drug having at least one ionized group in
IPR2014-00654
Patent 6,340,475 B2

12
the pH range 5 through 8. Id. We remain unpersuaded to narrow our
reading of claim 1 based upon Patent Owner’s assertion that a person of
ordinary skill in the art would understand that the release of a highly soluble
drug, as recited by claim 1, occurs only by a diffusion-controlled
mechanism.
Indeed the Specification describes, “[t]he invention is also of use with
drugs that have been formulated to include additives that impart a small
degree of hydrophobic character, to further retard the release rate of the drug
into the gastric fluid.” Ex. 1001, 7:44–47. As Petitioner and its declarant
assert, claim 1 of the ’475 patent does not preclude the use of an additive.
Pet. Reply 9 (citing Ex. 1042 ¶¶ 33–34). Thus, if the use of such an additive
results in dissolution-controlled drug release for a high solubility drug, as
Patent Owner asserts, we are not persuaded that the Specification limits the
invention of claim 1 to diffusion-controlled drug release. See, e.g., Ex. 2015
¶ 154 (explaining that such an additive confers dissolution control to a
highly soluble drug).
For similar reasons, we are not persuaded that claim 43 is limited to
diffusion-controlled or erosion-controlled drug release. As with claim 1,
claim 43 does not preclude the use of an additive to retard the release rate of
a highly soluble drug and render it a dissolution-controlled drug release
mechanism. Thus, we are not persuaded that the Specification expressly
disclaims drug release mechanisms other than those controlled by diffusion
or erosion.
Finally, Patent Owner argues that a person of ordinary skill in the art
would have understood the plain and ordinary meaning of the claims to
require that “dissolution of the drug triggers the ultimate drug release
IPR2014-00654
Patent 6,340,475 B2

13
according to the claimed rate-controlling mechanism, which is diffusion for
the Product Claims, and diffusion or erosion for the Method Claims.” PO
Resp. 19–20; Ex. 2015 ¶¶ 71–72.
Petitioner’s declarant, Dr. Wilson, testifies otherwise, explaining a
person of ordinary skill in the art would understand the plain and ordinary
meaning of the claims is simply that—at least both dissolution and diffusion
contribute to drug release for claim 1 and at least dissolution and diffusion or
dissolution and erosion contribute to drug release for claim 43. Ex. 1042
¶¶ 9–10. Dr. Wilson also explained that Banker & Rhodes describes a
system that utilizes a combination of diffusion and dissolution with a
swelling-controlled matrix. Id. ¶¶ 18–19. In particular, Banker & Rhodes
describes such a system as one where the polymer swells and “allows
entrance of water, which causes dissolution of the drug and diffusion out of
the swollen matrix. In these systems the release rate is highly dependent on
the polymer-swelling rate, drug solubility, and the amount of soluble
fraction in the matrix.” Ex. 1025, 590. Thus, according to the Banker &
Rhodes treatise, drug formulations using a “swelling-controlled” matrix may
release drugs by “dissolution of the drug and diffusion out of the swollen
matrix,” wherein variable factors may control the rate of release. Id. In
other words, contrary to Patent Owner’s assertions, claiming a “controlled
release drug” and referring to drug release by “dissolution and diffusion”
does not necessarily mean the drug release must be controlled by either
dissolution or diffusion.
Upon considering the arguments and evidence, we determine that the
broadest reasonable interpretation of (1) “releases said drug . . . by the
dissolution and diffusion of said drug out of said matrix” is “releases the
IPR2014-00654
Patent 6,340,475 B2

14
drug by dissolution of the drug in the matrix followed by diffusion of the
drug out of the matrix”; and (2) “releases said drug into gastric fluid by the
dissolving of said drug by said gastric fluid and either erosion of said matrix
or diffusion of said dissolved drug out of said matrix” is “releases the drug
into gastric fluid by dissolving the drug by the gastric fluid followed by
erosion of the matrix or diffusion of the dissolved drug out of the matrix.”
B. Principles of Law
To prevail in this inter partes review of the challenged claims,
Petitioner must prove unpatentability by a preponderance of the evidence.
35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d).
A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
differences between the claimed subject matter and the prior art are such that
the subject matter, as a whole, would have been obvious at the time the
invention was made to a person having ordinary skill in the art to which said
subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved on the basis of underlying
factual determinations, including: (1) the scope and content of the prior art;
(2) any differences between the claimed subject matter and the prior art;
(3) the level of skill in the art; and (4) objective evidence of nonobviousness.
Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
“[A] patent composed of several elements is not proved obvious
merely by demonstrating that each of its elements was, independently,
known in the prior art.” KSR, 550 U.S. at 418. “[I]t can be important to
identify a reason that would have prompted a person of ordinary skill in the
relevant field to combine elements in the way the claimed new invention
does.” Id. Moreover, a person of ordinary skill in the art must have had a
IPR2014-00654
Patent 6,340,475 B2

15
reasonable expectation of success of doing so. PAR Pharm., Inc. v. TWi
Pharms., Inc., 773 F.3d 1186, 1193 (Fed. Cir. 2014).
We analyze the instituted grounds of unpatentability in accordance
with the above-stated principles.
C. The Level of Ordinary Skill in the Art
In large part, the parties agree as to the level of ordinary skill in the
art. Pet. 9–10; PO Resp. 13. Both agree that a person of ordinary skill in the
art would be a person with at least a bachelor’s degree in chemistry,
chemical engineering, pharmaceutical science, and/or material science, as
well as substantial experience in development of controlled release oral
dosage forms involving polymeric materials. Pet. 9–10; PO Resp. 13. In
light of the parties’ general agreement, we adopt that description of the level
of ordinary skill in the art for purposes of this proceeding. In our analysis,
we consider the applied prior art as representative of the level of ordinary
skill in the art.
D. Obviousness over Baveja, the ’548 Patent, the Shell 1993 Publication,
and the Shell ’790 Patent
Petitioner asserts that claims 1, 2, 8, 9, 13–15, 61, and 62 of the ’475
patent are unpatentable as obvious over Baveja, the ’548 patent, the Shell
1993 publication, and the Shell ’790 patent. Pet. 21–35; Pet. Reply 7–13.
Patent Owner disagrees. PO Resp. 20–39.
1. Baveja
Baveja discloses a dosage form comprised of a swellable hydrophilic
matrix that exhibits zero-order (i.e., constant) release of a drug. Ex. 1008,
Summary. Baveja uses β-adrenergic blockers propranolol hydrochloride,
alprenolol hydrochloride, and metoprolol tartrate as model drugs. Id. at 40.
Baveja describes tablets with different ratios of HPMC, sodium
IPR2014-00654
Patent 6,340,475 B2

16
carboxymethylcellulose (“Na CMC”), and drug, which are then subjected to
an in vitro dissolution study. The in vitro dissolution study involves placing
the tablets into a dissolution rate test apparatus with diluted HCl (pH 3.0) for
three hours and then in 0.2 M phosphate buffer (pH 7.4) for another 9 hours.
Id.
The results of the dissolution studies for tablets formed from just
HPMC and drug are shown in Figures 1–3. For example, Figure 2 is
reproduced below:

Figure 2 illustrates the cumulative percent of metoprolol tartrate
released as a function of time from tablets containing metoprolol tartrate to
HPMC in the ratios shown. Id. at 41.
As explained by Baveja, the rate of release of the tablets made of drug
and HPMC decreases with time, which may be due to “an increase in
diffusional path length for the drug[,] which in turn may be due to slower
erosion rate of the rubbery layer and faster advancement of swelling front
into the glassy polymer.” Id.
IPR2014-00654
Patent 6,340,475 B2

17
Baveja also describes tablets formed from HPMC, Na CMC, and drug
in varying amounts that exhibit a nearly zero-order rate of release. Id.,
Summary.
2. The ’548 Patent
The ’548 patent relates to a controlled-release dosage form
comprising a drug and at least two different cellulose ethers. Ex. 1006,
1:12–16. According to the ’548 patent specification, “[an] object of the
present invention is to provide a dosage form of delivering a drug in the
gastrointestinal tract that substantially avoids a premature disintegration.”
Id. at 3:1–4. The ’548 patent specification also states that the disclosed
invention “delivers a drug at a rate of dosage form release that corresponds
to the rate of change of the integrity of the dosage form over a prolonged
period of at least eight hours.” Id. at 3:4–7.
Moreover, the dosage form uses cellulose ethers, which swell
extensively when hydrated and lessen direct drug contact with mucosal
tissues. Id. at 11:23–26. The drug delivery matrix is suitable for gastric
retention over the releasing lifetime of the dosage system. Id. at 10:65–68.
Furthermore, “when all the drug is released, the system bioerodes into
innocuous particles and dissolved polymers that pass from the
gastrointestinal tract.” Id. at 10:68–11:3.
3. Shell 1993 Publication
The Shell 1993 publication discloses a sustained-release oral drug
dosage form that releases a solution of a drug into the stomach and that
comprises a tablet or capsule of a plurality of particles of a solid-state drug
dispersed in alkyl cellulose. Ex. 1007, 2:13–17. The alkyl cellulose “swells
unrestricted dimensionally via imbibition of gastric fluid to increase the size
IPR2014-00654
Patent 6,340,475 B2

18
of the particles . . . with consequent increase in gastric retention time of the
particles.” Id. at 2:17–21. The dosage form also “permits dissolution of the
dispersed drug by imbibed gastric fluid while the drug is within the particle
and release of the resulting solution” and “maintains its physical integrity
over at least a substantial portion of the time period during which the drug is
released into the stomach and then dissolves.” Id. at 2:23–31.
4. Shell ’790 Patent
The Shell ’790 patent discloses a sustained-release oral dosage form
that “is retained well in the stomach and releases drug as a solution into the
stomach.” Ex. 1005, 1:6–9. The dosage form comprises a plurality of solid
particles composed of a solid-state drug dispersed within a hydrophilic,
water-swellable polymer that swells in gastric fluid to increase the particle
size to a level that promotes retention in the stomach over the time period.
Id. at 1:54–60. The dosage form also “permits slow dissolution of the
dispersed drug by gastric fluid and release of the resulting solution from the
particles.” Id. at 1:60–63. Finally, the dosage form “maintains its physical
integrity over at least a substantial portion of the time period and thereafter
rapidly dissolves.” Id. at 1:65–67.
5. Analysis
Based on our review of the arguments and evidence presented by both
parties, we conclude that Petitioner has not shown by a preponderance of the
evidence that claims 1, 2, 8, 9, 13–15, 61, and 62 are unpatentable as
obvious over the cited references.
Petitioner argues that each limitation of claim 1 is disclosed in at least
one of the four cited references. Pet. 23–28. For example, Petitioner notes
that each reference discloses controlled-release oral drug dosage forms
IPR2014-00654
Patent 6,340,475 B2

19
comprising a polymeric matrix. Id. at 23; see also Ex. 1008, Summary; Ex.
1006, 1:12–19; Ex. 1007, 2:13–17; Ex. 1005, 1:54–58. Petitioner also
asserts that the Shell 1993 publication discloses a dosage form when swollen
is of a size that appears to promote retention in the stomach in the fed move.
Pet. 24; Ex. 1007, 2:13–34. Petitioner asserts that the Shell 1993 publication
discloses that the release rate of the drug is by dissolution and diffusion.
Pet. 24–25; see also Ex. 1007, 7:2–6 (“The release rate of the drug(s) from
the particles is primarily dependent upon the rate at which the drug(s) is
leached from the particles, which in turn is related to the dissolution rate of
the drug, the particle size and drug concentration in the particle.”).
Petitioner also states that Figures 1 and 2 of Baveja disclose drug release
studies in which the dosage forms retained at least 40% of the drug after one
hour and released at least 80% of the drug after immersion in gastric fluid.
Pet. 26; see also Ex. 1008, Figs. 1–2. Finally, Petitioner notes that at least
the Shell ’790 patent discloses a dosage form that remains substantially
intact until substantially all of the drug is released. Pet. 28; Ex. 1005, 2:60–
67 (stating “the polymer maintains its integrity (i.e., it does not significantly
or appreciably dissolve, erode or otherwise decompose or degrade) over at
least a substantial portion (i.e., at least about 90% and preferably over 100%)
of the intended dosing period”).
Based on the evidence presented above, we are persuaded that
Petitioner has shown that each limitation of claim 1 is separately disclosed
by at least one of the cited references. Our analysis, however, does not end
there. A patent “is not proved obvious merely by demonstrating that each of
its elements was, independently, known in the prior art.” KSR, 550 U.S. at
418. Petitioner must also show that there was a reason to combine those
IPR2014-00654
Patent 6,340,475 B2

20
elements to achieve the claimed invention with a reasonable expectation of
success. See PAR Pharm., 773 F.3d at 1193. To make that determination,
we can look to “interrelated teachings of multiple patents; the effects of
demands known to the design community or present in the marketplace; and
the background knowledge possessed by a person having ordinary skill in
the art.” KSR, 550 U.S. at 418. We can also look to the nature of the
problem to be solved. In re Gartside, 203 F.3d 1305, 1319 (Fed. Cir. 2000)
(holding that suggestion to combine “may come from, inter alia, the
teachings of the references themselves and, in some cases, from the nature of
the problem to be solved”). After considering the parties’ arguments and
evidence, however, we are not persuaded that Petitioner has shown by a
preponderance of the evidence that a person of ordinary skill would have
combined the teachings in the manner recited by the claims with a
reasonable expectation of success.
Petitioner argues that a person of ordinary skill in the art with
knowledge of Baveja, the ’548 patent, the Shell 1993 publication, and the
Shell ’790 patent would have known how to make a dosage form containing
all the elements of claim 1 of the ’475 patent. Pet. 22 (citing Ex. 1011
¶¶ 174–184). In particular, Petitioner contends that a person of ordinary
skill in the art would have been motivated to combine the teachings of the
cited art because all of the references “are intended to solve the same
problem; that is, the controlled release of a drug.” Id.; Pet. Reply 12–13
(citing Ex. 1042 ¶¶ 75, 79). As such, Petitioner argues that a person of
ordinary skill in the art reading Baveja would look to the other references
“for further examples of formulations that would be compatible with the
teachings of Baveja.” Pet. 22. According to Petitioner’s declarant, Dr.
IPR2014-00654
Patent 6,340,475 B2

21
Wilson, a person of ordinary skill in the art would have understood that the
matrices and release profiles disclosed in the ’548 patent and Shell 1993
publication were also appropriate for use in a sustained-release drug dosage
form such as those disclosed in Baveja. Ex. 1011 ¶ 181. Finally, Petitioner
argues that a person of ordinary skill in the art would have been motivated to
combine the cited references because they have interrelated teachings. Pet.
23 (citing Ex. 1011 ¶ 182); Pet. Reply 12 (citing Ex. 1042 ¶¶ 76–77, 80).
For example, Petitioner states that all of the references relate to controlled
release oral drug dosage forms and each describes polymer matrices that
swell when hydrated. Pet. 23; Pet. Reply 12.
Upon considering the full trial record, however, we find Petitioner’s
arguments to be overly vague and nonspecific. Although it is true that our
obviousness approach should be “expansive and flexible,” KSR, 550 U.S. at
415, “patents are not barred just because it was obvious ‘to explore a new
technology or general approach that seemed to be a promising field of
experimentation, where the prior art gave only general guidance as to the
particular form of the claimed invention or how to achieve it.’” Procter &
Gamble Co. v. Teva Pharms USA, Inc., 566 F.3d 989, 997 (Fed. Cir. 2009)
(quoting In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)).
Thus, even though the references may have interrelated teachings and
are intended to solve the same problem of controlled drug release, Petitioner
has not explained persuasively how or why a person of ordinary skill in the
art would have combined the various features of the cited prior art references
in the manner recited by the claims. Indeed, Petitioner has not even
explained what features of which references a person of ordinary skill in the
IPR2014-00654
Patent 6,340,475 B2

22
art would have combined to derive the claimed invention and why that
person would have done so.
Given the numerous possible combinations of references, during oral
argument, the panel asked counsel for Petitioner which references Petitioner
really needs for its obviousness challenge:
JUDGE HULSE: . . . . Do you really need all four of
these references to make out your case?
[COUNSEL FOR PETITIONER]: No, Your Honor, we
do not.
JUDGE HULSE: Which would you primarily rely on?
[COUNSEL FOR PETITIONER]: Shell ’93, Your
Honor. If we were asked that question, we think Shell ’93,
together with one or any of the – would render these claims
obvious.
Tr. 28:16–23.
But even if we were to focus on the Shell 1993 publication, we are
still not persuaded that Petitioner has met its burden. We agree with Patent
Owner that the Shell 1993 publication does not teach a dosage form that
“releases substantially all of said drug [after immersion in gastric fluid].”
PO Resp. 36 (citing Ex. 2015 ¶¶ 149–51). According to the broadest
reasonable interpretation of this limitation, Petitioner must show that the
Shell 1993 publication teaches a dosage form that releases “at least 80% of
said drug” after immersion in gastric fluid. Petitioner has failed to do so.
Petitioner relies on Example 1 and Figure 1 as disclosing this limitation.
Pet. 27 (citing Ex. 1007, Example 1, Figure 1). Figure 1, which illustrates
the results of Example 1, is reproduced below:
IPR2014-00654
Patent 6,340,475 B2

23

Figure 1 depicts the percentage of aspirin released over time for the various
drug formulations tested, including conventional aspirin without
hydroxypropylcellulose. Ex. 1007, 13–14.
As an initial matter, claim 1 requires that the dosage form release
“substantially all of said drug” after immersion in gastric fluid. The “said
drug” of claim 1 is a drug “whose solubility in water is greater than one part
by weight of said drug in ten parts by weight of water.” Petitioner has not
shown that the aspirin tested in Example 1 of the Shell 1993 publication
satisfies this solubility requirement. Moreover, even if aspirin were highly
soluble, Figure 1 does not show that any of the dosage forms (other than
conventional aspirin) released at least 80% of the drug over the course of the
seven-hour experiment.
3
Ex. 1007, Fig. 1; see also id. at 13–14. Thus, we

3
The “conventional” dosage form tested is a tablet of aspirin without
hydroxypropylcellulose. Ex. 1007, 13–14.
IPR2014-00654
Patent 6,340,475 B2

24
find that the Shell 1993 publication does not teach a dosage form that
“releases substantially all of said drug.”
We agree with Petitioner, however, that at least Baveja and the Shell
’790 patent teach a dosage form that does satisfy this limitation.
4
Pet. 27
(citing Ex. 1008, Fig. 1; Ex. 1005, Example 2). Despite this determination,
however, it is unclear which reference or combination of references
Petitioner contends a person of ordinary skill in the art would rely on to
modify the dosage form of the Shell 1993 publication. That is, Petitioner
does not explain persuasively why or how a person of ordinary skill in the art
would modify the drug formulation of the Shell 1993 publication in view of
Baveja and/or the Shell ’790 patent to develop a drug formulation that
releases at least 80% of a highly soluble drug. See InTouch Techs., Inc. v.
VGO Commc’ns, Inc., 751 F.3d 1327, 1351 (Fed. Cir. 2014) (reversing
district court’s judgment of invalidity where expert’s testimony “was vague
and did not articulate reasons why a person of ordinary skill in the art at the
time of the invention would combine these references”).
Nor are we persuaded that Petitioner has shown by a preponderance of
the evidence that a person of ordinary skill in the art would have had a
reasonable expectation of success in combining the drug formulations of the
cited references. As Patent Owner notes, Petitioner’s declarant testified
about several formulation considerations that impact drug release. PO Resp.

4
Petitioner also argues that “Example 3 of the ’548 patent describes a
dosage form that releases approximately 80% of its ibuprofen after eight
hours.” Pet. 27 (citing Ex. 1006, Example 3, Fig. 6). We, however, are not
persuaded that the ’548 patent teaches this limitation, because Petitioner has
not directed us to evidence that ibuprofen is a highly soluble drug.
IPR2014-00654
Patent 6,340,475 B2

25
23. Such considerations include the drug to polymer ratio (Ex. 2023, 78:17–
23), type of polymer used (id. at 79:24–80:5), and particle size (id. at 99:10–
100:15). Dr. Wilson also testified that formulating a reliable gastric
retentive controlled release dosage form is “very difficult.” Ex. 2023,
101:10–15. Given this testimony from Petitioner’s own declarant, we credit
the testimony of Patent Owner’s declarant, Dr. Hopfenberg, that “[m]atrices
formulated with a given polymer in a dosage form can result in different
release controlling mechanisms, depending on the details of the matrix
formulation and drug solubility characteristics.” Ex. 2015 ¶ 164.
Accordingly, we find that Petitioner does not address sufficiently why a
person of ordinary skill in the art would believe it could modify the
formulation of the Shell 1993 publication to incorporate the drug release
profile of Baveja and/or the Shell ’790 patent without, for example, affecting
the other desired properties of the Shell 1993 publication formulation (e.g.,
the swelling in a dimensionally unrestricted manner to a size that promotes
gastric retention).
Furthermore, establishing persuasively a reasonable expectation of
successfully combining elements known in the art first requires some clear
articulation of that combination, which, as explained above, is missing when
examined through the lens of the full trial record. Petitioner has not
identified any combinations of the cited references that would be most
promising to try. Instead, Petitioner’s declarant makes conclusory assertions
that “it would be natural for a [person of ordinary skill in the art] to combine
the teachings of these references” and that a person of ordinary skill in the
art would have expected success in combining the references because that
IPR2014-00654
Patent 6,340,475 B2

26
person “would be focused on the characteristics necessary to achieve those
goals.” Ex. 1042 ¶¶ 80–81.
In contrast, Patent Owner’s declarant, Dr. Hopfenberg, credibly
explains why a person of ordinary skill in the art would not have a
reasonable expectation of success in combining the references. For
example, Dr. Hopfenberg testifies that a person of ordinary skill in the art
would expect the drug release characteristics of Baveja to change if the
disclosed dosage forms were reformulated to remain substantially intact.
Ex. 2015 ¶ 180. Dr. Hopfenberg also explains that a person of ordinary skill
in the art reading the Shell 1993 publication would not modify that dosage
form according to the Shell ’790 patent. Ex. 2015 ¶ 166. Dr. Hopfenberg
explains that the Shell 1993 publication is described as an “improvement” of
the formulation of the Shell ’790 patent. Id. (quoting Ex. 1007, 1:20–22).
Specifically, Dr. Hopfenberg notes that, unlike the polymers in the ’790
patent, the polymers described in the Shell 1993 publication are not
crosslinked and are “inherently safer.” Id. (quoting Ex. 1007, 1:30–32).
Thus, we are persuaded that Petitioner has not established by a
preponderance of the evidence that the prior art would have guided a person
of ordinary skill in the art to combine prior art elements in a manner that
would have yielded the claimed invention. See, e.g., In re Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litigation, 676 F.3d 1063,
1071 (Fed. Cir. 2012) (describing a proposed combination of known
elements without direction or guidance regarding “which of many possible
choices is likely to be successful” as involving impermissible hindsight)
(quoting In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009)).
IPR2014-00654
Patent 6,340,475 B2

27
We agree with Patent Owner that Petitioner’s obviousness challenge
amounts to picking and choosing certain preferred attributes of the various
references and combining them to yield the claimed invention. PO Resp. 1–
2. We are also persuaded by Dr. Hopfenberg’s testimony that such a
piecemeal combination reflects impermissible hindsight. See, e.g., Ex. 2015
¶ 178 (“Only in hindsight can the preferred attributes of Baveja and the ’548
Patent be selectively retained and combined with the desired integrity of
Shell 1993 Pub. and the Shell ’790 Patent dosage form.”); see Cheese Sys.,
Inc. v. Tetra Pak Cheese and Powder Sys., Inc., 725 F.3d 1341, 1352 (Fed.
Cir. 2013) (“Obviousness ‘cannot be based on the hindsight combination of
components selectively culled from the prior art to fit the parameters of the
patented invention.’”) (citation omitted).
Accordingly, after considering the arguments and evidence, we
determine that Petitioner has not shown by a preponderance of the evidence
that claims 1, 2, 8, 9, 13–15, 61, and 62 of the ’475 patent are unpatentable
as obvious over Baveja, the ’548 patent, the Shell 1993 publication, and the
Shell ’790 patent.
E. Obviousness of Claims 43, 57, 58, and 66 over the Shell 1993
Publication, Baveja, and Colombo
Petitioner asserts that claims 43, 57, 58, and 66 of the ’475 patent are
unpatentable as obvious over the Shell 1993 Publication, Baveja, and
Colombo. Pet. 35–43; Pet. Reply 7–13. Patent Owner disagrees. PO Resp.
39–46. We incorporate here our earlier findings and discussion regarding
the disclosures of the Shell 1993 Publication and Baveja.
1. Colombo
Colombo relates to swellable matrix systems in the form of a tablet
comprising a mixture of the drug diltiazem, HPMC, ethylcellulose, and
IPR2014-00654
Patent 6,340,475 B2

28
mannitol. Ex. 1009, 44. Colombo discloses three different matrices:
Case 0, the plain matrix; Case 1, the matrix coated with cellulose acetate
propionate (“CAP”) on one face; and Case 2, the matrix coated with CAP on
both faces. Id. Colombo describes “[s]welling and release experiments” in
which the matrices were swollen in deionized water, and the drug release
measurements were obtained concomitantly with the matrix swelling
observations. Id.
Colombo describes and depicts the morphological changes in the
matrices over time, observing that, in the uncoated system (Case 0), “[v]ery
quickly (after 15 min) the swelling of the matrix moves both in axial and
radial directions.” Id. Colombo also discloses the drug release profiles of
the systems. Id. at 45. Figure 5 of Colombo is reproduced below:

Figure 5 depicts the fraction of diltiazem released over time for the
Case 0, Case 1, and Case 2 matrices.
2. Analysis
Petitioner argues that each limitation of claims 43, 57, 58, and 66 is
taught by at least one of the Shell 1993 publication, Baveja, or Colombo.
See Pet. 27, 42–45. However, for reasons similar to those explained above,
IPR2014-00654
Patent 6,340,475 B2

29
we are not persuaded that Petitioner has shown, by a preponderance of the
evidence, that a person of ordinary skill in the art would have had a reason to
combine the references to achieve the inventions of claims 43, 57, 58, and
66 with a reasonable expectation of success. In other words, Petitioner has
not articulated reasoning with rational underpinnings to support a motivation
to combine the teachings of the prior art. KSR, 550 U.S. at 417–418 (citing
In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)).
Accordingly, after considering the arguments and evidence, we
determine that Petitioner has not shown by a preponderance of the evidence
that claims 43, 57, 58, and 66 are unpatentable as obvious over the Shell
1993 publication, Baveja, and Colombo.
F. Secondary Considerations of Nonobviousness
In light of our determination that Petitioner has not shown by a
preponderance of the evidence that any of the challenged claims are
unpatentable as obvious, we need not reach the merits of Patent Owner’s
evidence of secondary considerations of nonobviousness.
MOTIONS TO EXCLUDE EVIDENCE III.
Both parties filed motions to exclude evidence offered by the
opposing side. The party moving to exclude evidence bears the burden of
proving that it is entitled to the relief requested—namely, that the material
sought to be excluded is inadmissible under the Federal Rules of Evidence
(“FRE”). See 37 C.F.R. §§ 42.20(c), 42.62(a). We address each party’s
motion in turn.
1. Petitioner’s Motion to Exclude Evidence
Petitioner moves to exclude Exhibits 2163 and 2165, which are a
textbook chapter and a journal article, under FRE 401, 402, and 403. Paper
IPR2014-00654
Patent 6,340,475 B2

30
52. Because we did not rely on either of these exhibits or any testimony
associated with these exhibits in reaching our Decision here, we dismiss
Petitioner’s motion to exclude as moot.
2. Patent Owner’s Motion to Exclude Evidence
Patent Owner moves to exclude claim charts from the copending
district court litigation (Ex. 1015) and corresponding testimony relying on
the claim charts, as irrelevant and prejudicial under FRE 401, 402, and 403.
Paper 54, 2–4. We do not rely on Exhibit 1015 or any of the corresponding
testimony in reaching our Decision here. Accordingly, we dismiss Patent
Owner’s motion to exclude this evidence as moot.
Patent Owner also moves to exclude (1) the declaration and report of
Dr. Kinam Park (Exhibits 1019 and 1029), and corresponding testimony
relying on those exhibits as unreliable expert opinion (Paper 54, 1–2); and
(2) allegedly new opinions raised by Dr. Wilson in his Reply Declaration
(Ex. 1042) (Paper 54, 4–10). Patent Owner’s arguments, however, go to the
weight of the evidence presented, and not to the admissibility. As explained
above, we accorded Dr. Park’s test results little to no weight. And as for the
allegedly new opinions of Dr. Wilson, to the extent any evidence was
improperly presented, we have declined to rely on it in reaching our
Decision. Regardless, we need not reach the merits of Patent Owner’s
motion to exclude because even considering the disputed evidence,
Petitioner has not shown by a preponderance of the evidence that any of the
claims are unpatentable as obvious. Accordingly, Patent Owner’s motion to
exclude this evidence is dismissed as moot.
IPR2014-00654
Patent 6,340,475 B2

31
CONCLUSION IV.
We conclude that Petitioner has not shown by a preponderance of the
evidence that claims 1, 2, 8, 9, 13–15, 43, 57, 58, 61, 62, and 66 of the ’475
patent are unpatentable under 35 U.S.C. § 103.
ORDER V.
In consideration of the foregoing, it is hereby:
ORDERED that claims 1, 2, 8, 9, 13–15, 43, 57, 58, 61, 62, and 66 of
the ’475 patent are not held unpatentable;
FURTHER ORDERED that Petitioner’s Motion to Exclude Evidence
is dismissed;
FURTHER ORDERED that Patent Owner’s Motion to Exclude
Evidence is dismissed; and
FURTHER ORDERED that, because this is a Final Written Decision,
the parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

IPR2014-00654
Patent 6,340,475 B2

32
PETITIONER:
Bruce C. Haas
Henry J. Renk
Stephen K. Yam
Christopher Hill
FITZPATRICK, CELLA, HARPER & SCINTO
endo-ipr@fchs.com
endo-ipr@fchs.com
syam@fchs.com
chill@fchs.com

PATENT OWNER:
Arlene L. Chow
Eric J. Lobenfeld
Peter H. Noh
Ernest Yakob
HOGAN LOVELLS US LLP
arlene.chow@hoganlovells.com
eric.lobenfeld@hoganlovells.com
peter.noh@hoganlovells.com
ernest.yakob@hoganlovells.com