DEPOMED, INC. v. PURDUE PHARMA L.P. et al
Filing
277
MEMORANDUM OPINION filed. Signed by Judge Mary L. Cooper on 4/6/2017. (mmh)
NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
:
DEPOMED, INC.,
:
:
Plaintiff,
:
v.
:
:
PURDUE PHARMA L.P., THE P.F.
:
LABORATORIES, INC. and PURDUE :
PHARMACEUTICALS L.P.,
:
:
Defendants.
:
:
CIVIL ACTION NO. 13-571 (MLC)(TJB)
MEMORANDUM OPINION
Cooper, District Judge
OUTLINE
PRELIMINARY STATEMENT
I.
BACKGROUND
A.
B.
The asserted ‘475 and ‘280 Patents
The disputed claim terms
1.
2.
3.
4.
5.
6.
II.
“Gastric fluid”
“Remains substantially intact”
“Until all of said drug is released”
Claim terms concerning swelling upon imbibition of water or gastric
fluid
Claim terms concerning “substantially all of said drug”
Claim terms concerning poly(ethylene oxide) molecular weights
DISCUSSION
1
A.
B.
C.
Legal standard
Definition of the person of ordinary skill in the art
Application
1.
2.
3.
4.
5.
6.
III.
“Gastric fluid”
“Remains substantially intact”
“Until all of said drug is released”
Claim terms concerning swelling upon imbibition of water or gastric
fluid
Claim terms concerning “substantially all of said drug”
Claim terms concerning poly(ethylene oxide) molecular weights
CONCLUSION
PRELIMINARY STATEMENT
This is a claim construction opinion in a patent infringement action. The plaintiff,
Depomed, Inc. (“Depomed”), has sued defendants Purdue Pharma L.P., The P.F.
Laboratories, Inc., and Purdue Pharmaceuticals L.P. (collectively, “Purdue”) for patent
infringement pursuant to 35 U.S.C. § 271(a). Depomed alleges that Purdue’s controlledrelease oxycodone pain-relief drug product, sold under the brand name OxyContin®,
infringes claims of U.S. Patent Nos. 6,340,475 (“the ‘475 Patent”) and 6,635,280 (“the
‘280 Patent”) (together, “the patents-in-suit”).1 The patents-in-suit do not claim
oxycodone hydrochloride, the active ingredient in OxyContin®, or the treatment of pain.
They are directed to compositions and methods for the controlled delivery of a dosage
form to the stomach and upper gastrointestinal (“GI”) system.
1
Initially, Depomed also alleged that Purdue’s OxyContin® product infringed U.S.
Patent Nos. 6,723,340 (“the ‘340 Patent”) and 8,329,215 (“the ‘215 Patent”). However, the
parties subsequently agreed to dismiss, with prejudice, all claims and defenses with respect to the
‘340 and ‘215 Patents.
2
The parties submitted a Joint Claim Construction and Prehearing Statement in
which they report agreement as to the meaning of six claim terms common to both
patents-in-suit, one claim term exclusive to the ‘475 Patent, and one claim term exclusive
to the ‘280 Patent. (See dkt. 121-1.)2 The parties propose constructions for twelve
disputed claim terms. (See id.) Seven claim terms are common to both patents-in-suit,
two claim terms are exclusive to the ‘475 Patent, and three claim terms are exclusive to
the ‘280 Patent. The twelve disputed claim terms can be organized into the following six
categories: (1) “gastric fluid”; (2) “remains substantially intact”; (3) “until all of said drug
is released”; (4) claim terms concerning swelling upon imbibition of water or gastric
fluid; (5) claim terms concerning “substantially all of said drug”; and (6) claim terms
concerning poly(ethylene oxide) molecular weights. We adopt and utilize these six
categories below, when discussing the disputed claim terms.
I.
BACKGROUND
A.
The asserted ‘475 and ‘280 Patents
The ‘475 Patent and the ‘280 Patent, both entitled “Extending the Duration of
Drug Release Within the Stomach During the Fed Mode,” were issued to Depomed as
assignee on January 22, 2002 and October 21, 2003, respectively.3 The ‘280 Patent is a
2
The Court will cite to the documents filed on the Electronic Case Filing System
(“ECF”) by referring to the docket entry numbers by the designation “dkt.” Pincites reference
ECF pagination.
3
The ‘475 Patent is Exhibit 1 to the Amended Complaint. (See dkt. 49-1 at 1-25.) The
‘280 Patent is Exhibit 2 to the Amended Complaint. (See dkt. 49-1 at 26-51.) Copies of both
patents-in-suit are also attached as exhibits to various Markman papers submitted by the parties.
We will simply cite those patents by page, drawing sheet, or column and line number.
3
continuation of the application that issued as the ‘475 Patent.4 The patents-in-suit both
descend from U.S. Patent Application No. 08/870,509 (“the ‘509 Application”), filed on
June 6, 1997, now abandoned.5
The patents-in-suit6 are directed to compositions and methods for the controlled
delivery of a dosage form to the stomach and upper GI system. The Background section
explains that conventional drug tablets or capsules can release a drug too quickly when
they come into contact with bodily fluids. ‘475 Pat., col. 1, ll. 30-33. This may result in
transient overdoses followed by a long period of underdosing. Id., col. 1, ll. 33-35. Such
a delivery pattern is undesirable and of limited clinical usefulness. Id., col 1, ll. 35-36.
In addition, drugs in tablet or other dosage forms have a tendency to pass from the
stomach into the small intestine after the conclusion of the fed mode7 with some drug
4
The prosecution histories of the patents-in-suit were not supplied to the Court. The
parties do not rely on the prosecution histories to support their respective claim construction
positions. Thus, a detailed summary of the prosecution histories of the patents-in-suit does not
follow.
5
Purdue did submit excerpts of the prosecution history of the ‘509 Application. (See
dkt. 133-2 at 122-223.)
6
The ‘475 and ‘280 Patents share a common written description. Thus, when describing
the contents of the common written description, we cite only the written description of the ‘475
Patent for convenience. We may also refer to the common written description as only “the
written description” for convenience.
7
The fed mode or postprandial mode is the digestive state. It is distinguishable from the
interdigestive state (or fasting mode) by distinct patterns of gastroduodenal motor activity, which
determine the gastric retention of the stomach contents. See ‘475 Pat., col. 11, ll. 23-30. The fed
mode may be characterized as follows:
The postprandial or fed mode is induced by food ingestion, and
begins with a rapid and profound change in the motor pattern of the
upper GI tract, the change occurring over a period of 30 seconds to
one minute. The stomach generates 3-4 continuous and regular
4
remaining in the tablet or dosage form. Id., col. 2, ll. 17-29. This may result in a loss of
effectiveness with drugs that provide their maximum benefit when absorbed in the
stomach and upper GI tract. Id., col. 2, ll. 29 – col. 5, ll. 25.
The patents-in-suit address these problems, as well as others, by presenting a
“formulation in which the drug is dispersed in a polymeric matrix that is water-swellable
rather than merely hydrophilic, that has an erosion rate that is substantially slower than its
swelling rate, and that releases the drug primarily by diffusion.” Id., col. 5, ll. 58-62.
The patents-in-suit explain that “the rate of diffusion of the drug out of the matrix can be
slowed by increasing the drug particle size, by the choice of polymer used in the matrix,
and/or by the choice of molecular weight of the polymer.” Id., col. 5, ll. 63-66. The
invention generally operates as follows:
The matrix . . . swells upon ingestion, preferably to a size that
is at least about twice its unswelled volume, and that promotes
gastric retention during the fed mode. . . . The penetrating fluid
then causes release of the drug in a gradual and prolonged
manner by the process of solution diffusion, i.e., dissolution of
the drug in the penetrating fluid and diffusion of the dissolved
drug back out of the matrix. The matrix itself is solid prior to
contractions per minute, similar to those of the interdigestive mode
but of about half the amplitude. The change occurs almost
simultaneously at all sites of the GI tract, before the stomach
contents have reached the distal small intestine. Liquids and small
particles flow continuously from the stomach into the small
intestine. Contractions of the stomach result in a sieving process
that allows liquids and small particles to pass through a partially
open pylorus. Indigestible particles greater than the size of the
pylorus are retropelled and retained in the stomach. Particles
exceeding about 1 cm in size are thus retained in the stomach for
approximately 4 to 6 hours.
‘475 Pat., col. 11, l. 53 – col. 12, l. 2. A description of the characteristics of the fasting mode is
also provided in the written description. See ‘475 Pat., col. 11, ll. 31-52.
5
administration and, once administered, remains undissolved in
(i.e., is not eroded by) the gastric fluid for a period of time
sufficient to permit the majority of the drug to be released by
the solution diffusion process during the fed mode. The ratelimiting factor in the release of the drug is therefore controlled
diffusion of the drug from the matrix rather than erosion,
dissolving or chemical decomposition of the matrix.
For highly soluble drugs, the swelling of the polymeric matrix
thus achieves two objectives—(i) the tablet swells to a size
large enough to cause it to be retained in the stomach during
the fed mode, and (ii) it retards the rate of diffusion of the
highly soluble drug long enough to provide multi-hour,
controlled delivery of the drug into the stomach. For drugs that
are either sparingly soluble, of limited solubility, or of high
solubility, . . . the swelling of the polymeric matrix (i) renders
the matrix sufficiently large to cause retention in the stomach
during the fed mode, and (ii) localizes the release of the drug
to the stomach and small intestine so that the drug will have its
full effect without colonic degradation, inactivation, or loss of
bioavailability.
Id., col. 5, l. 66 – col. 6, l. 33.
The written description explains that the “water-swellable polymer forming the
matrix . . . is any polymer that is non-toxic, that swells in a dimensionally unrestricted
manner upon imbibition of water, and that provides for sustained release of an
incorporated drug.” Id., col. 7, ll. 54-58. Polyalkylene oxides are a class of suitable
matrix polymers for use in the invention. See id., col. 7, l. 58 – col. 8, l. 29.
Poly(ethylene oxide) is a preferred polyalkylene oxide, according to the written
description:
A particularly preferred polyalkylene oxide is poly(ethylene
oxide), which term is used herein to denote a linear polymer of
unsubstituted ethylene oxide. Poly(ethylene oxide) polymers
having molecular weights of about 4,000,000 and higher are
preferred. More preferred are those with molecular weights
6
within the range of about 4,500,000 to about 10,000,000, and
even more preferred are polymers with molecular weights
within the range of about 5,000,000 to about 8,000,000.
Id., col. 8, ll. 31-40. The amount of polymer relative to the drug may vary depending on
the desired drug release rate, the polymer itself, the molecular weight of the polymer, and
excipients present in the formulation. Id., col. 9, ll. 22-25. However, the polymer must
be sufficient to retain a portion of the drug within the matrix one hour after ingestion (or
immersion in gastric fluid):
The amount of polymer will be sufficient however to retain at
least about 40% of the drug within the matrix one hour after
ingestion (or immersion in the gastric fluid). Preferably, the
amount of polymer is such that at least 50% of the drug remains
in the matrix one hour after ingestion. More preferably, at least
60%, and most preferably at least 80%, of the drug remains in
the matrix one hour after ingestion.
Id., col. 9, ll. 25-32. The drug will be “substantially all released from the matrix within
about ten hours, and preferably within about eight hours, after ingestion, and the
polymeric matrix will remain substantially intact until all of the drug is released.” Id.,
col. 9, ll. 33-36. The term “substantially intact” is explicitly defined in the written
description to mean “a polymeric matrix in which the polymer portion 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.” Id., col. 9, ll. 36-41.
The written description sets forth multiple preferred dosage forms in accordance
with the invention. Gelatin capsules containing either two or three pellets of drug
impregnated polymer are described in detail by size and shape. See id., col. 10, ll. 20-31.
Single, elongated tablets are also described in a similar manner. See id., col. 10, ll. 317
38. The written description does not provide specific shapes or dimensions that these
dosage forms will swell to. The swollen size is generally described in functional terms.
See, e.g. id., abstract (“hydrophilic polymers the swell upon imbibition of water to a size
that is large enough to promote retention of the dosage form in the stomach during the fed
mode”); col. 5, l. 66 – col. 6, l. 3 (“The matrix is a relatively high molecular weight
polymer that swells upon ingestion, preferably to a size that is at least about twice its
unswelled volume, and that promotes gastric retention during the fed mode”); col. 9, ll. 15 (“The hydrophilicity and water swellability of these polymers cause the drugcontaining matrices to swell in size in the gastric cavity due to ingress of water in order to
achieve a size that will be retained in the stomach when introduced during the fed
mode”).
8
The written description also provides multiple examples illustrating the controlledrelease behavior of various dosage forms,8 the sustained release of a dosage form,9 and
differences between subjects in the fed mode and subjects not in the fed mode in terms of
gastric retention of tablets of various sizes administered orally.10
With respect to the ‘475 Patent, claims 1, 11-15, 43, and 55 are relevant to this
dispute, and are reproduced in the margin.11 With respect to the ‘280 Patent, claims 1,
8
Example 1 illustrates the controlled-release behavior of metformin hydrochloride from
a polymeric matrix consisting of poly(ethylene oxide) in three different dose systems designed to
release 90% of their drug contents at approximately 3 hours, 6 hours, or 8 hours. See ‘475 Pat.,
col. 12, l. 10 – col. 13, l. 8; Fig. 1. Example 2 illustrates the controlled-release behavior of
captopril from a polymeric matrix consisting of poly(ethylene oxide), both with and without
glyceryl monostearate. See id., col. 13, ll. 10-38; Fig. 2. Example 3 illustrates the controlledrelease behavior of captopril from a polymeric matrix of hydroxyethyl cellulose with the
inclusion of glyceryl monostearate at varying pellet sizes. See id., col. 13, ll. 40-63; Fig. 3.
Example 4 illustrates the controlled release of metformin hydrochloride, using a higher drug
loading, and various polymers and combinations of polymers. See id., col. 13, l. 66 – col. 13, l.
36; Fig. 4. Example 5 illustrates the controlled release of metformin hydrochloride from a single
capsule-shaped tablet. See id., col. 14, ll. 39-50; Fig. 5. Example 6 further illustrates the
controlled release of captopril, using various polymers and combinations of polymers. See id.,
col. 14, l. 53 – col. 15, l. 40; Fig. 6. Example 7 presents further data on metformin
hydrochloride formulations, illustrating the effect of lower drug loadings than those used in
Examples 1, 4, and 5. See id., col. 15, ll. 42-59; Fig. 7. Example 10 further illustrates the
controlled release of metformin hydrochloride from a single capsule-shaped tablet. See id., col.
17, ll. 26-37; Fig. 9.
9
Example 8 illustrates the sustained release of vancomycin hydrochloride from various
polymers. See id., col. 15, l. 62 – col. 16, l. 41.
10
Example 9 illustrates the difference between subjects (both Beagle dogs and humans)
in the fed mode and subjects not in the fed mode in terms of the gastric retention of tablets of
various sizes administered orally. See id., col. 16, l. 43 – col. 17, l. 23.
11
Claim 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 about 15:85 to about 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
9
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 all of said drug is released.
Claim 11. A dosage form of claim 1 in which said polymeric matrix is formed of
poly(ethylene oxide) at a molecular weight in the range of about 4,500,000 to about 10,000,000.
Claim 12. A dosage form of claim 1 in which said polymeric matrix is formed of
poly(ethylene oxide) at a molecular weight in the range of about 5,000,000 to about 8,000,000.
Claim 13. A dosage form of claim 1 in which said polymeric matrix upon immersion in
gastric fluid retains at least about 50% of said drug one hour after such immersion.
Claim 14. A dosage form of claim 1 in which said polymeric matrix upon immersion in
gastric fluid retains at least about 60% of said drug one hour after such immersion.
Claim 15. A dosage form of claim 1 in which said polymeric matrix upon immersion in
gastric fluid retains at least about 80% of said drug one hour after such immersion.
Claim 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
(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.
Claim 55. A method in accordance with claim 43, in which said solid polymeric matrix
comprises poly(ethylene oxide) at a molecular weight of from about 4,500,000 to about
10,000,000.
‘475 Pat., col. 17, ll. 45-59; col. 18, ll. 21-35; col. 25, ll. 39-64 (emphasis added).
10
11-15, 43, and 45-46 are relevant to this dispute, and are also reproduced in the margin.12
The disputed claim terms are bolded and will be discussed in more detail in Section I.B,
infra.
12
Claim 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 one or more polymers forming a solid polymeric matrix with said
drug incorporated therein at a weight ratio of drug to polymer of from 15:85 to 80:20, said
dosage form being one that when swollen in a dimensionally unrestricted manner as a result
of imbibition of water is of a size exceeding the pyloric diameter in the fed mode 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 after such immersion, and that remains
substantially intact until substantially all of said drug is released.
Claim 11. A dosage form in accordance with claim 1 in which said polymeric matrix is
formed of poly(ethylene oxide) at a molecular weight in the range of about 4,500,000 to about
10,000,000.
Claim 12. A dosage form in accordance with claim 1 in which said polymeric matrix is
formed of poly(ethylene oxide) at a molecular weight in the range of about 5,000,000 to about
8,000,000.
Claim 13. A dosage form in accordance with claim 1 in which said polymeric matrix
upon immersion in gastric fluid retains at least about 50% of said drug one hour after such
immersion.
Claim 14. A dosage form in accordance with claim 1 in which said polymeric matrix
upon immersion in gastric fluid retains at least about 60% of said drug one hour after such
immersion.
Claim 15. A dosage form in accordance with claim 1 in which said polymeric matrix
upon immersion in gastric fluid retains at least about 80% of said drug one hour after such
immersion.
Claim 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 one or more polymers
forming a solid polymeric matrix with said drug incorporated therein at a weight ratio of drug to
polymer of from 0.01:99.99 to 80:20, said polymeric matrix being one that:
11
B.
The disputed claim terms
As discussed above, there are twelve claim terms in dispute. These terms are
organized into six categories: (1) “gastric fluid”; (2) “remains substantially intact”; (3)
“until all of said drug is released”; (4) claim terms concerning swelling upon imbibition
of water or gastric fluid; (5) claim terms concerning “substantially all of said drug”; and
(6) claim terms concerning poly(ethylene oxide) molecular weights. This section
summarizes the parties’ proposed constructions for the claim terms in dispute. This
section also provides, when applicable, a brief summary of the claim construction history
for these terms. Many of the terms at issue here were previously construed by multiple
district courts and the Patent Trials and Appeal Board (“PTAB”).
(a) when swollen in a dimensionally unrestricted manner as a result of imbibition of
gastric fluid is of a size exceeding the pyloric diameter in the fed mode 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) protects any unreleased drug in said matrix from said gastric fluid,
(d) retains at least about 40% of said drug one hour after such immersion in gastric fluid,
and
(e) releases substantially all of said drug within about ten hours after such
immersion,
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.
Claim 45. A dosage form in accordance with claim 1 in which said dosage form releases
substantially all of said drug within about ten hours after immersion in gastric fluid.
Claim 46. A dosage form in accordance with claim 1 in which said dosage form releases
substantially all of said drug within about eight hours after immersion in gastric fluid.
‘280 Pat., col. 17, ll. 45-61; col. 18, ll. 24-43; col. 25, ll. 36-62; col. 26, ll. 24-29 (emphasis
added).
12
1.
“Gastric fluid”
The claim term “gastric fluid” appears in claims 1, 13-15, and 43 of the ‘475
Patent and claims 1, 13-15, 43, 45, and 46 of the ‘280 Patent. See nn. 8, 9, supra. The
parties’ respective constructions are as follows:
Term Identified for
Construction
“gastric fluid”
Depomed’s Proposed
Construction
“both the fluid in the
stomach and simulated or
artificial fluids recognized
by those skill[ed] in the art
as a suitable model for the
fluid of the human
stomach”
Purdue’s Proposed
Construction
“Encompasses both fluid in
the human stomach, and
any simulated or artificial
fluids recognized by those
skilled in the art as a
suitable model for the fluid
of the human stomach.”
(Dkt. 121-1 at 13-15.) The dispute between the parties is whether the term “gastric fluid”
is limited to mean only fluid in the human stomach. This claim term has been construed
by three district courts and in three inter partes review (“IPR”) proceedings.13
In Depomed, Inc. v. Ivax Corp., No. C 06-00100, 2006 WL 3782829 (N.D. Cal.
December 20, 2006) (hereinafter “Ivax”), Judge Charles R. Breyer concluded that the
term “gastric fluid” was “entitled to a broad construction that encompasses both the fluid
in the human stomach, and any simulated or artificial fluids recognized by those skilled
in the art as a suitable model for the fluid of the human stomach.” Id. at *8. The two
13
The PTAB may construe patent claims during an IPR proceeding. The PTAB
interprets claim terms in an unexpired patent according to their 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, 1275-79 (Fed. Cir. 2015), aff’d sub nom. Cuozzo
Speed Techs., LLC v. Lee, 136 S. Ct. 2131 (2016). The PTAB’s constructions are not binding
on this Court.
13
other district courts construed the term to mean “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.” See Depomed, Inc. v. Sun Pharma Global FZE, No. 113553, 2012 WL 3201962 (D.N.J Aug. 3, 2012) (hereinafter “Sun”)14; Depomed, Inc. v.
Lupin Pharmaceuticals, Inc., No. C 09-5587, 2011 WL 1877984, at *9 (N.D. Cal. May
17, 2011) (hereinafter “Lupin”). In all three of the IPR proceedings, the parties agreed to
apply the construction from the Sun and Lupin cases. (See dkt. 132-9; dkt. 132-10; dkt.
132-11; dkt. 132-12; dkt. 132-13; dkt. 132-14.)
2.
“Remains substantially intact”
The claim term “remains substantially intact” appears in claims 1 and 43 of the
‘475 Patent and claim 1 of the ‘280 Patent. See nn. 8, 9, supra. The parties’ respective
constructions are as follows:
Term Identified for
Construction
“remains substantially
intact”
Depomed’s Proposed
Construction
“A polymeric matrix in
which the polymer portion
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”
14
Purdue’s Proposed
Construction
“A polymeric matrix in
which the swollen polymer
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”
In Sun, the court noted that the parties agreed on the term “gastric fluid,” and therefore
no further construction was necessary. Sun, 2012 WL 3201962, at *9. The Sun Court’s Order
construing the term “gastric fluid” may be found at Depomed, Inc. v. Sun Pharma Global FZE,
No. 11-3553, 2012 WL 9514228, at *1 (D.N.J. Aug. 3, 2012).
14
(Dkt. 121-1 at 26-27.) The dispute between the parties is whether the “substantial
intactness” is limited to a specific portion of the matrix. This claim term has been
construed by two district courts and in three IPR proceedings. The construction adopted
by the court in Lupin, which was agreed to by the parties in that case, is identical to the
construction proposed by Depomed here. See Lupin, 2011 WL 1877984, at *16. Judge
Pisano’s construction in Depomed, Inc. v. Actavis Elizabeth LLC, Nos. 12-1358, 122813, 2014 WL 316702 (D.N.J. Jan. 28, 2014) (hereinafter “Actavis”), is also identical to
Depomed’s proposed construction. See id. at *10. In the IPR proceedings, Purdue did
not propose a construction for this claim term. In all three proceedings, the PTAB
adopted Depomed’s proposed construction, which is identical to the one proposed here.
(See dkt. 132-9, dkt. 132-10, dkt. 132-11, dkt. 132-12, dkt. 132-13, dkt. 132-14.)
3.
“Until all of said drug is released”
The claim term “until all of said drug is released” appears in claims 1 and 43 of
the ‘475 Patent. See n. 8, supra. The parties’ respective constructions are as follows:
Term Identified for
Construction
“until all of said drug is
released”
Depomed’s Proposed
Construction
“until the plateau of the
dissolution profile
characterizing drug release
from the swollen dosage
form is reached”
Purdue’s Proposed
Construction
“100% of the drug has been
released”
(Dkt. 121-1 at 24-26.) The dispute between the parties is over the amount of drug that
must be released to constitute “all” of the drug being released. This claim term has been
construed by two district courts and in two IPR proceedings. In Sun and Lupin, this
claim term was construed to mean “until the plateau of the dissolution profile
15
characterizing drug release from the swollen dosage form is reached,” the same
construction Depomed advocates for here. See Sun, 2012 WL 3201962, at *12; Lupin,
2011 WL 1877984, at *11-13. However, in two of the IPR proceedings between the
parties, the PTAB rejected the construction Depomed proposes here, and instead
construed the term to have its plain, ordinary meaning. (See dkt. 132-12 at 8-10; dkt.
132-14 at 8-10.)
4.
Claim terms concerning swelling upon imbibition of water or
gastric fluid
The following claim terms concern the swelling of the dosage form upon
imbibition of water or gastric fluid. The claim term “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” appears in claim 1 of the ‘475 Patent. See
n. 8, supra. The claim term “said polymeric matrix being one that swells upon imbibition
of gastric fluid to a size large enough to promote retention in the stomach during said fed
mode” appears in claim 43 of the ‘475 Patent. See id. These claim terms are very
similar, and the parties each propose a single construction for both terms. These terms
differ with respect to the type of imbibition fluid (i.e., water vs. gastric fluid) and some
additional minor language. The parties’ respective constructions are as follows:
16
Term Identified for
Construction
“said polymeric matrix
being one the swells upon
imbibition of water thereby
attaining a size large
enough to promote
retention in the stomach
during said fed mode”
“said polymeric matrix
being one that swells upon
imbibition of gastric fluid
to a size large enough to
promote retention in the
stomach during said fed
mode”
Depomed’s Proposed
Construction
“the dosage form, which
comprises a polymeric
matrix, increases in size
due to the ingress of
[water/gastric fluid], such
that when the dosage form
is introduced into the
stomach in the fed mode,
the dosage form remains in
the stomach for several
hours”
Purdue’s Proposed
Construction
“The polymeric matrix of
the oral drug dosage form
increases in size upon
imbibition of water to a
size exceeding 9.5 mm
diameter x 9.5 mm length,
such that when the dosage
form is introduced into the
stomach during the fed
mode, it remains in the
stomach for at least 4
hours”
(Dkt. 121-1 at 9-11.)
The claim term “when swollen in a dimensionally unrestricted manner as a result
of imbibition of [water/gastric fluid] is of a size exceeding the pyloric diameter in the fed
mode to promote retention in the stomach during said fed mode” appears in claims 1 and
43 of the ’280 Patent.15 See n. 9, supra. The parties’ respective constructions are as
follows:
15
Claim 1 of the ‘280 Patent recites “imbibition of water,” and claim 43 of the ‘280
patent recites “imbibition of gastric fluid.”
17
Term Identified for
Construction
“when swollen in a
dimensionally unrestricted
manner as a result of
imbibition of [water/gastric
fluid] is of a size exceeding
the pyloric diameter in the
fed mode to promote
retention in the stomach
during said fed mode”
Depomed’s Proposed
Construction
“‘when swollen in a
dimensionally unrestricted
manner as a result of
imbibition of [water/gastric
fluid]’ is given its plain and
ordinary meaning”
Purdue’s Proposed
Construction
“The dosage form, which
comprises a polymeric
matrix, increases in size
upon imbibition of
[water/gastric fluid] to a
size exceeding 9.5 mm
diameter x 9.5 mm length,
“‘is of a size exceeding the such that when the dosage
pyloric diameter in the fed form is introduced into the
mode to promote retention stomach during the fed
in the stomach during said mode, it remains in the
fed mode’ means ‘such that stomach for at least 4
when the dosage form is
hours”
introduced into the stomach
in the fed mode, the dosage
form remains in the
stomach for several hours”
(Dkt. 121-1 at 11-13.)
In Lupin, Judge Hamilton construed the terms “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” and “said dosage form being one that
when swollen in a dimensionally unrestricted manner as a result of imbibition of water is
of a size exceeding the pyloric diameter in the fed mode to promote retention in the
stomach during the fed mode” together to mean “the dosage form, which comprises a
polymeric matrix, increases in size due to the ingress of water, such that when the dosage
form is introduced into the stomach in the fed mode, the dosage form remains in the
stomach for several hours.” Lupin, 2011 WL 1877984, at *5-9. The dispute in the Lupin
case regarding these claim terms involved whether the polymeric matrix swells in an
“unrestricted” manner, and whether the polymeric matrix remains “solid” when it swells.
18
See id., at *6. Those disputes are different than the disputes we are asked to address, i.e.,
limitations as to the size of the swollen matrix and the time the dosage form remains in
the stomach.16
The Court in Sun adopted an identical construction for these terms, noting that the
parties agreed to Judge Hamilton’s construction from Lupin during their Markman
hearing. See Sun, 2012 WL 3201962, at *8.
In Ivax, Judge Breyer construed the terms “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” and “said dosage form being one that
when swollen in a dimensionally unrestricted manner as a result of imbibition of water is
of a size exceeding the pyloric diameter in the fed mode to promote retention in the
stomach during the fed mode” together to mean that “the drug dosage form’s polymeric
matrix increases in size, and does not erode, such that when introduced to a stomach in
the fed mode, the dosage form remains in the stomach for several hours.” Ivax, 2006 WL
3782829, at *14. Judge Breyer articulated the “crucial question” to be “how large the
swollen dosage form must be in order to ‘promote retention.’” Id. at *12. Depomed
proposed that a swollen size of 8 mm would be appropriate. Id. at *13. Ivax argued that
a numeric boundary was not required, but offered a range between 2 mm to 20 mm, if
one must be determined. Id. at *12. Judge Breyer declined to impose a minimum size of
16
The Court notes that in Lupin, Lupin originally proposed a size limitation for the
swollen matrix of “at least 20% greater than that of the starting tablet,” but withdrew that
limitation in a responsive brief. See Lupin, 2011 WL 1877984, at *5.
19
the swollen dosage form necessary to promote retention, because there was an “absence
of compelling intrinsic or extrinsic evidence indicating that a specific size would be
sufficient to promote retention.” Id. at *13. The Court reasoned that:
A patentee has the right to claim the invention in terms that
would be understood by persons of skill in the art, and
“mathematical precision should not be imposed for its own
sake.” [Modine Mfg. Co. v. U.S. Intern. Trade Comm’n, 75
F.3d 1545, 1557 (Fed. Cir. 1996)]. A person of skill in the art
reading the patent as a whole would recognize that the claimed
polymer matrices must swell upon absorption of water, and
must not significantly erode throughout the relevant period of
immersion in gastric fluid. Moreover, a person of skill in the
art would recognize that the patent discloses that a tablet of a
given composition and of 4 mm in size would perform as
claimed—that is, such a dosage form attained a size that is
“large enough to promote retention” in the subjects that were
studied. See ‘475 patent at 17:9–24. From this basic teaching,
one of skill in art would understand both the requirements and
the means for testing for compliance with the claim
requirements. The Court declines to impose a more specific
construction of the disputed claim terms, especially since tying
the scope of the disputed claim to a minimum size that is
supported primarily by the result from one example would
impermissibly read a limitation into the claims.
Id.
In Actavis, Judge Pisano construed the term “thereby attaining a size large enough
to promote retention in the stomach during said fed mode” and “is of a size exceeding the
pyloric diameter in the fed mode to promote retention in the stomach during said fed
mode” together to mean “such that when the dosage form is introduced into the stomach
in the fed mode, the dosage form remains in the stomach for several hours.” Actavis,
2014 WL 316702, at *3-5. In Actavis, neither party advocated for a construction that
included a size limitation. In that case, the dispute focused on the duration of the
20
retention of the dosage form in the stomach. Depomed’s proposed construction was
“temporal,” requiring the drug to remain in the stomach for “several hours.” Actavis’
proposed construction was “functional,” requiring the dosage form to remain in the
stomach until the entirety of the drug is delivered. See id. at *4. Judge Pisano adopted
Depomed’s construction, relying on the discussion of drug retention in terms of time, not
drug delivery. See id. at *5. Judge Pisano did not, and was not asked to, define a specific
amount of time, as the parties ask us to do here. Judge Pisano also declined to construe
the term “said dosage form being one that when swollen in a dimensionally unrestricted
manner as a result of imbibition of water.” See id. at *8-9. He rejected “any limitation
on the rate or extent of swelling, so long as there is swelling of the dimension of the
dosage form” and found that the term’s plain and ordinary meaning should apply. Id. at
*8-9.
5.
Claim terms concerning “substantially all of said drug”
The following five claim terms concern the release of “substantially all of said
drug” from the dosage form. For each of these claim terms, Purdue does not propose a
construction, and instead contends that they are indefinite. (See dkt. 133 at 16-27; dkt.
159 at 12-22.)
The claim term “releases substantially all of said drug within about eight hours
after such immersion” appears in claim 1 of the ‘475 Patent and claim 46 of the ‘280
Patent. See nn. 8, 9, supra. Depomed’s proposed construction is as follows:
21
Term Identified for
Construction
“releases substantially all
of said drug within about
eight hours after such
immersion”
Depomed’s Proposed
Construction
“at least 80% of the drug
has been released after
eight hours of immersion in
gastric fluid”
(Dkt. 121-1 at 15-17.)
The claim term “releases substantially all of said drug after such immersion”
appears in claim 1 of the ‘280 Patent. See n. 9, supra. Depomed’s proposed construction
is as follows:
Term Identified for
Construction
“releases substantially all
of said drug after such
immersion”
Depomed’s Proposed
Construction
“at least 80% of the drug
has been released after
immersion in gastric fluid”
(Dkt. 121-1 at 17-18.)
The claim term “releases substantially all of said drug within about ten hours after
such immersion” appears in claim 43 of the ‘475 Patent and claims 43 and 45 of the ‘280
Patent. See nn. 8, 9, supra. Depomed’s proposed construction is as follows:
Term Identified for
Construction
“releases substantially all
of said drug within about
ten hours after such
immersion”
Depomed’s Proposed
Construction
“at least 80% of the drug
has been released after ten
hours of immersion in
gastric fluid”
(Dkt. 121-1 at 19-20.)
The claim term “until substantially all of said drug is released” appears in claim 1
of the ‘280 Patent. See n. 9, supra. Depomed’s proposed construction is as follows:
22
Term Identified for
Construction
“until substantially all of
said drug is released”
Depomed’s Proposed
Construction
“at least 80% of the drug
has been released”
(Dkt. 121-1 at 20-22.)
The claim term “while releasing substantially all of said drug within said stomach
where said drug is maintained in an acidic environment” appears in claim 43 of the ‘475
Patent and claim 43 of the ’280 Patent. See nn. 8, 9, supra. Depomed’s proposed
construction is as follows:
Term Identified for
Construction
“while releasing
substantially all of said
drug within said stomach
where said drug is
maintained in an acidic
environment”
Depomed’s Proposed
Construction
“at least 80% of the drug
has been released after
immersion in gastric fluid”
(Dkt. 121-1 at 22-24.)
The five claim terms identified above, or portions thereof, have been construed by
three district courts and in multiple IPR proceedings. The district courts that have been
asked to construe these terms have consistently construed the phrase “substantially all of
said drug” to mean “at least 80% of the drug.” See Sun, 2012 WL 3201962, at *9-11
(construing the terms “releases substantially all of said drug within about eight hours
after such immersion,” “until substantially all of said drug is released,” and “while
releasing substantially all of said drug within said stomach where said drug is maintained
in an acidic environment” to mean “at least 80% of the drug has been released after eight
hours of immersion in gastric fluid”); Lupin, 2011 WL 1877984, at *11 (construing
23
“releases substantially all of said drug within about eight hours after such immersion” to
mean “at least 80% of the drug has been released after eight hours of immersion in gastric
fluid” and “until substantially all of said drug is released” means “at least 80% of the
drug has been released after eight hours of immersion in gastric fluid” per the parties’
agreement); Ivax, 2006 WL 3782829, at *4-5 (construing the term “releases substantially
all of said drug within about eight hours after such immersion” to mean that “at least 80%
of the drug has been released after eight hours”). The PTAB has also adopted similar, if
not identical, constructions. (See dkt. 132-9, dkt. 132-10, dkt. 132-11, dkt. 132-12, dkt.
132-13, dkt. 132-14.)
6.
Claim terms concerning poly(ethylene oxide) molecular weights
The following two claim terms concern the molecular weight of the poly(ethylene
oxide) used to form the polymeric matrix.
The claim term “about 4,500,000 to about 10,000,000” appears in claims 11 and
55 of the ‘475 Patent and claim 11 of the ‘280 Patent. See nn. 8, 9, supra. The parties’
respective constructions are as follows:
Term Identified for
Construction
“about 4,500,000 to about
10,000,000”
Depomed’s Proposed
Construction
“Plain and ordinary
meaning”
Purdue’s Proposed
Construction
“4,275,000 to 10,500,000”
(Dkt. 121-1 at 28.)
The claim term “about 5,000,000 to about 8,000,000” appears in claim 12 of the
‘475 Patent and claim 12 of the ‘280 Patent. See nn. 8, 9, supra. The parties’ respective
constructions are as follows:
24
Term Identified for
Construction
“about 5,000,000 to about
8,000,000”
Depomed’s Proposed
Construction
“Plain and ordinary
meaning”
Purdue’s Proposed
Construction
“4,750,000 to 8,400,000”
(Dkt. 121-1 at 28-29.)
As far as the Court is aware, these claim terms have not previously been the
subject of claim construction.
II.
DISCUSSION
A.
Legal standard
“It is a ‘bedrock principle’ of patent law that ‘the claims of a patent define the
invention to which the patentee is entitled the right to exclude.’” Phillips v. AWH Corp.,
415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc) (quoting Innova/Pure Water Inc. v. Safari
Water Filtration Sys., Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). Claim construction
determines the correct claim scope, and is a determination exclusively for the court as a
matter of law. Markman v. Westview Instruments, Inc., 52 F.3d 967, 978-79 (Fed. Cir.
1995) (en banc), aff’d, 517 U.S. 370 (1996). The focus in construing disputed terms in
claim language “is on the objective test of what one of ordinary skill in the art at the time
of the invention would have understood the term[s] to mean.” Id. at 986.
To determine the meaning of the claims, courts start by considering the intrinsic
evidence. Phillips, 415 F.3d at 1313; C.R. Bard, Inc. v. U.S. Surgical Corp., 388 F.3d
858, 861 (Fed. Cir. 2004); Bell Atl. Network Servs., Inc. v. Covad Commc’ns Group,
Inc., 262 F.3d 1258, 1267 (Fed. Cir. 2001). The intrinsic evidence includes the claims
25
themselves, the specification, and the prosecution history. Phillips, 415 F.3d at 1314;
C.R. Bard, Inc., 388 F.3d at 861.
The claims themselves provide substantial guidance in determining the meaning of
particular claim terms. Phillips, 415 F.3d at 1314. First, the context in which a term is
used in the asserted claim can be very instructive. Id. Other asserted or unasserted
claims can aid in determining the claim’s meaning because claim terms are normally used
consistently throughout a patent. Id. Differences among claims can also assist in
understanding a term’s meaning. Id. For example, when a dependent claim adds a
limitation, there is a presumption that the independent claim does not include that
limitation. Id. at 1314-15.
“[C]laims ‘must be read in view of the specification of which they are a part.’” Id.
at 1315 (quoting Markman, 52 F.3d at 979). “[T]he specification ‘is always highly
relevant to the claim construction analysis. Usually, it is dispositive; it is the single best
guide to the meaning of a disputed term.’” Id. (quoting Vitronics Corp. v. Conceptronic,
Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). This is true because a patentee may define his
own terms, give a claim term a different meaning than the term would otherwise possess,
or disclaim or disavow the claim scope. Id. at 1316. In these circumstances, the
inventor’s lexicography governs. Id. The specification may also resolve the meaning of
ambiguous claim terms “where the ordinary and accustomed meaning of the words used
in the claims lack sufficient clarity to permit the scope of the claim to be ascertained from
the words alone.” Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1325 (Fed. Cir.
2002). But, “[a]lthough the specification may aid the court in interpreting the meaning of
26
disputed claim language, particular embodiments and examples appearing in the
specification will not generally be read into the claims.” Comark Commc’ns, Inc. v.
Harris Corp., 156 F.3d 1182, 1187 (Fed. Cir. 1998) (quoting Constant v. Advanced
Micro-Devices, Inc., 848 F.2d 1560, 1571 (Fed. Cir. 1988)); accord Phillips, 415 F.3d at
1323.
The prosecution history is another tool to supply the proper context for claim
construction. It “can often inform the meaning of the claim language by demonstrating
how the inventor understood the invention and whether the inventor limited the invention
in the course of prosecution, making the claim scope narrower that it would otherwise
be.” Phillips, 415 F.3d at 1317.
“Extrinsic evidence consists of all evidence external to the patent and prosecution
history, including expert and inventor testimony, dictionaries, and learned treatises.”
Markman, 52 F.3d at 980. Although extrinsic evidence can be useful, it is “less
significant than the intrinsic record in determining ‘the legally operative meaning of
claim language.’” Phillips, 415 F.3d at 1317 (quoting C.R. Bard, Inc., 388 F.3d at 862).
Dictionaries and treatises may aid a court in understanding the underlying
technology and the manner in which one skilled in the art might use claim terms, but
dictionaries and treatises may provide definitions that are too broad or may not be
indicative of how the term is used in the patent. Id. at 1318. Similarly, expert testimony
may aid a court in understanding the underlying technology and determining the
particular meaning of a term in the pertinent field, but an expert’s conclusory,
unsupported assertions as to a term’s definition are entirely unhelpful to a court. Id.
27
Generally, extrinsic evidence is “less reliable than the patent and its prosecution
history in determining how to read claim terms.” Id. The Supreme Court recently
explained the role of extrinsic evidence in claim construction:
In some cases, however, the district court will need to look
beyond the patent’s intrinsic evidence and to consult extrinsic
evidence in order to understand, for example, the background
science or the meaning of a term in the relevant art during the
relevant time period. . . . In cases where those subsidiary facts
are in dispute, courts will need to make subsidiary factual
findings about that extrinsic evidence. These are the
“evidentiary underpinnings” of claim construction that we
discussed in Markman, and this subsidiary factfinding must be
reviewed for clear error on appeal.
Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831, 841 (2015).
As is sometimes the case, the claim terms requiring construction may have been
the subject of prior claim construction proceedings by other district courts, or even the
same court. While rulings of the Federal Circuit on issues of claim construction for a
given patent are binding on later district courts analyzing the same patent, interpretations
of the same or other district courts of the same terms in the patent or patent family are
generally not binding. See Shire Dev. LLC v. Amneal Pharms. LLC, Civ. No. 15-2865,
2016 WL 4119940, at *2 (D.N.J. Aug. 2, 2016); see also Ravo v. Tyco Healthcare Group
LP, Civ. No. 11-1637, 2013 WL 3326657, at *6 (W.D. Pa. Mar. 13, 2013). However, the
interpretations of the same or other district courts are generally considered to be highly
relevant and persuasive authority. Shire, 2016 WL 4119940, at *2.
Overall, in construing the claims, “[t]he judge’s task is not to decide which of the
adversaries is correct. Instead, the judge must independently assess the claims, the
28
specification, and if necessary the prosecution history and relevant extrinsic evidence,
and declare the meaning of the claims.” Exxon Chem. Patents, Inc. v. Lubrizol Corp., 64
F.3d 1553, 1556 (Fed. Cir. 1995).
B.
Definition of the person of ordinary skill in the art
The parties’ experts, Dr. Leah Appel, Ph.D. (Depomed) and Dr. Jerry L. Atwood,
Ph.D. (Purdue), are well regarded and highly qualified to opine on the matters they did.
The proposed definitions for the person of ordinary skill in the art (“POSA”) offered by
the parties differ slightly.17 The second portion of Depomed’s definition includes the
definition set forth by Purdue. Neither party has lodged an objection with respect to these
definitions. Accordingly, the Court will adopt Depomed’s definition:
a person of ordinary skill in the art would have at least a
bachelor’s degree in the fields of chemistry, chemical
engineering, pharmaceutical science and/or material science
with a focus on polymer science, combined with substantial
experience in development of controlled release drug dosage
forms (even more desirably oral controlled release dosage
forms). Alternatively, if the person had obtained a Ph.D. in any
of the relevant fields, the required amount of industry
experience would decline to about two years.
(Dkt. 132-17 at 4.)
17
Dr. Appel defines the POSA as an individual having “at least a bachelor’s degree in the
fields of chemistry, chemical engineering, pharmaceutical science and/or material science with a
focus on polymer science, combined with substantial experience in development of controlled
release drug dosage forms (even more desirably oral controlled release dosage forms).” (Dkt.
132-17 at 4.) Dr. Appel also states, in the alternative, that “if the person had obtained a Ph.D. in
any of the relevant fields, the required amount of industry experience would decline to about two
years.” (Id.)
Dr. Atwood defines the POSA as an individual having “a Ph.D. degree in pharmaceutics,
chemistry or chemical engineering, along with at least two years of industrial experience in the
development of controlled-release oral dosage forms.” (Dkt. 133-1 at 4.)
29
C.
Application
We address the disputed claim terms according to the six categories discussed
above. We have reviewed the written submissions of the parties, and conducted a oneday claim construction hearing. (See dkt. 247, Markman Hr’g Tr.) The written
submissions of the parties with respect to the disputed claim terms are listed in the
margin.18
1.
“Gastric fluid”
For this claim term, each party adopts the construction reached in a previous claim
construction proceeding. See Section I.B.1, supra. Depomed adopts the construction
from both the Sun and Lupin cases verbatim. Purdue adopts the construction from the
Ivax case, removing only Judge Breyer’s preamble language that notes this term is
“entitled to a broad construction.” The difference between the parties’ constructions is
that Depomed’s construction of “gastric fluid” includes fluid from non-human animal
stomachs, whereas Purdue’s construction does not.
Depomed contends that a construction including fluid from non-human animal
stomachs is supported by the intrinsic evidence. Depomed points to the claims
themselves, arguing that they do not limit the type of gastric fluid that is covered.
Depomed also argues that the written description similarly does not make any distinction
18
Dkt. 121-1, Joint Claim Construction and Prehearing Statement; dkt. 132, Depomed’s
Opening Br.; dkt. 132-1 to dkt. 132-16, Andre I Decl.; dkt. 132-17 to dkt. 132-20, Appel I Decl.;
dkt. 133, Purdue’s Opening Br.; dkt. 133-1 to dkt. 133-3, Atwood Decl.; dkt. 133-4 to dkt. 133-5,
Walsh I Decl.; dkt. 159, Purdue’s Responsive Br.; dkt. 159-1 to dkt. 159-3, Walsh II Decl.; dkt.
161, Depomed’s Responsive Br.; dkt. 161-1 to 161-6, Lee Decl.; dkt. 161-7, Appel II Decl.
30
between animal gastric fluid and human gastric fluid for the purpose of the claimed
invention. In fact, Example 9 describes the testing of dosage forms in Beagle dogs in
both the fed mode and not in the fed mode. See ‘475 Pat., col. 16, l. 43 – col. 17, l. 24.
Depomed characterizes Purdue’s construction as an attempt to add a limitation that would
erroneously exclude the preferred canine gastric fluid embodiment of Example 9, which
is a suitable model for the fluid in the human stomach.
Depomed acknowledges that Purdue’s construction is the same as that in the Ivax
case. However, Depomed argues that the Ivax construction did not limit the term gastric
fluid to any specific type of gastric fluid. See Ivax, 2006 WL 3782829, at *7 (“The Court
concludes that, although the patent is directed toward a drug dosage form that is
ultimately for use in a patient, and therefore in the human stomach, the claims to the
composition are not necessarily limited to that milieu. . . .”).
Depomed’s expert, Dr. Leah Appel, Ph.D., declares that “gastric fluid” would
have been understood by a POSA to mean the fluid found in the gastrointestinal tract of
both humans and animals. (Dkt. 132-17 at 10.)19 Dr. Appel explains that animal tests are
19
Purdue contends that Depomed should not be allowed to rely on Dr. Appel’s
conclusions because she did not stand by the definition she proposed in her report at her
deposition. We do not rely on the extrinsic evidence to reach our construction of this claim term.
See Phillips, 415 F.3d at 1318 (indicating that use of extrinsic evidence in claim construction is
permissive, not mandatory (citing Markman, 52 F.3d at 980)). However, we note that we do not
agree with Purdue’s assertions that Dr. Appel abandoned the definition she proposed in her
report. She stated that she did not disagree with the construction of the Lupin and Sun cases, and
thought it was narrower than what she understood the term to encompass as a practicing
formulator. (See dkt. 159-2 at 9-10.) Importantly, when asked what the term “the stomach”
meant, Dr. Appel stated that it could be fluid in the stomach of a human and fluid in the stomach
of an animal. (Id. at 11.)
31
routinely performed by POSAs to understand how oral dosage forms will release drugs in
humans, and to determine their safety and efficacy. (Id.) In addition, POSAs may also
use a simulated gastric fluid to perform dissolution tests in vitro. (Id. at 11.)
Purdue contends that “gastric fluid” can only mean “human gastric fluid” or
“simulated human gastric fluid.” Purdue, relying on the testimony of its expert, Dr.
Atwood, argues that the description of simulated gastric fluid in the patent20 is for
simulated human gastric fluid. See dkt. 133-1 at 27. Purdue argues that since human
stomachs are the stomachs for the models, they are the only relevant stomachs to the
patents, and that it would not make sense for gastric fluid to encompass the gastric fluid
of non-human animals. Id. Purdue further contends that the patents-in-suit do not
describe drug dosage forms for any animals other than humans. Purdue argues that
Example 9 does not describe a preferred embodiment of the invention because there is no
drug in the dosage forms of Example 9, because that study was to demonstrate that the
tablets are retained in the stomach longer in the fed mode compared to the fasted mode.
The Court has considered the parties’ respective arguments and the relevant
evidence. The Court adopts Depomed’s proposed construction and construes the claim
term “gastric fluid” to mean “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.”
20
The fluid used in the in vitro test of Example 1 was a “modified simulated gastric
fluid” described as “7 mL of hydrochloric acid and 2 g of sodium chloride in 100 mL of
deionized water; the enzyme pepsin was omitted.” ‘475 Pat., col. 12, ll. 60-62.
32
There is no reason to limit the term “gastric fluid” to only “human gastric fluid.”
The term “gastric fluid” appears unmodified in the claims; and therefore, the claim
language itself does not restrict the scope of this term’s meaning. The term “stomach” is
also unmodified in the claims. The limitations referencing the stomach discuss the
properties that the dosage form must possess, e.g., the ability to attain a size large enough
to promote retention in the stomach during the fed mode. The claims do not restrict the
stomach to the human stomach, and therefore there is no inference that the term “gastric
fluid” must be limited to that of the human stomach.
The written description similarly does not restrict this claim term directly or by
inference. When describing a test subject, the written description repeatedly uses the
terms “patient” and “subject” without any further qualification. The term “human” only
appears twice in the entire written description. Both of those occurrences are found in the
discussion of Example 9, which, as discussed above, illustrates the differences between
human subjects and non-human animal subjects in various states. See ‘475 Pat., col. 16,
l. 43 – col. 17, 24. By including an example that discusses non-human animal test
subjects, the Court finds that the patentees did not intend to limit the term “gastric fluid”
to only human gastric fluid. For this term, the intrinsic evidence alone wholly supports
our construction. See Phillips, 415 F.3d at 1318 (Fed. Cir. 2005) (indicating that the use
of extrinsic evidence in claim construction is permissive, not mandatory (citing
Markman, 52 F.3d at 980)).
The Court is not persuaded by Purdue’s argument that Example 9 should not be
considered. Example 9 is concerned with one of the claimed aspects of the invention, the
33
retention of the dosage form in the stomach, and is therefore relevant regardless of
whether it has an incorporated drug or not.
Accordingly, the Court adopts Depomed’s proposed construction and construes
the claim term “gastric fluid” to mean “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.”
2.
“Remains substantially intact”
Depomed’s proposed construction for this claim term is taken verbatim from the
definition provided in the written description. See ‘475 Pat., col. 9, ll. 34-41 (“The term
‘substantially intact’ is used herein to denote a polymeric matrix in which the polymer
portion 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.”).
Depomed argues that this definition is dispositive and that Purdue’s proposed
construction improperly restricts the substantial intactness of the polymeric matrix to a
specific portion of the matrix, i.e., the “swollen” portion. Depomed also argues that the
written description discusses the polymeric matrix swelling in the context of the size that
it achieves, not as the portion of the matrix that remains intact.
Depomed’s expert, Dr. Appel, declares that the patentees’ definition for this term
is consistent with the meaning to a POSA, and that the intactness of the dosage form is
not restricted to any specific portion of the matrix. (See dkt. 132-17 at 22-23.) She
explained that:
34
A [POSA] understands that for a “polymeric matrix” to
“remain substantially intact” in the context of the patents,
means the polymeric matrix as a whole. This includes both the
swollen portion and the non-swollen portion of the “polymeric
matrix” that “remains substantially intact,” without necessarily
restricting the intactness to the swollen or to the non-swollen
portions in isolation.
(Id. at 23.)
Purdue contends that the swollen portion of the polymeric matrix must retain its
swollen size. Purdue, citing the written description, argues that the purpose of the
invention, i.e., controlling the location of the dosage form in the stomach, can only be
achieved if the polymer retains the size and shape of the swollen form and does not
disintegrate or break into small particles. (See dkt. 133 at 33-34.) Purdue’s expert, Dr.
Atwood, explains that “[t]he only way for the formulation to remain in the stomach and
not pass through the pylorus, in this scheme, is if the swollen polymer portion
substantially retains its size and shape. If the swollen portion deteriorates, then the
formulation will shrink back to the oral dosage form’s original size, which could pass
through the pylorus.” (Dkt. 133-1 at 28.) Because the swollen form is the essence of the
invention, according to Purdue, Purdue asks this Court to clarify that the swollen polymer
portion is what must substantially retain its size and shape.
The Court has considered the parties’ respective arguments and the relevant
evidence. The Court adopts Depomed’s proposed construction and construes the claim
term “remains substantially intact” to mean “a polymeric matrix in which the polymer
portion 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.”
35
The patentees provided a definition for this term in the specification. See ‘475
Pat., col. 9, ll. 34-41. That definition does not restrict the substantial intactness of the
polymeric matrix to a specific portion of the matrix. Generally, “[t]he patent’s
specification is the ‘single best guide to the meaning of a disputed term.’” Phillips, 415
F.3d at 1315 (quoting Vitronics, 90 F.3d at 1582). When an inventor defines a term in
the specification, “the inventor's lexicography governs.” Id. at 1316. Because the
applicants chose to be their own lexicographer, that definition shall govern. The Court is
unpersuaded by Purdue’s arguments, and declines to further limit the definition explicitly
provided by the patentees.
Accordingly, the Court construes the claim term “remains substantially intact” to
mean “a polymeric matrix in which the polymer portion 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.”
3.
“Until all of said drug is released”
For this term, the disagreement between the parties is over the amount of drug that
must be released to constitute “all” of the drug being released. As discussed above, the
two district courts that have construed this term have sided with Depomed. In Sun, Judge
Pisano acknowledged that “[t]he ‘475 Patent discloses that the dosage form will not
always, and often does not, release 100% of the incorporated drug,” but noted that there
was “nothing else in the intrinsic evidence to assist the Court in determining what
meaning the patentees intended to give ‘all of said drug.’” Sun, 2012 WL 3201962, at
*12. Judge Pisano ultimately adopted Depomed’s construction, relying on Judge
36
Hamilton’s construction in Lupin, the extrinsic evidence cited by Depomed, and
Depomed’s arguments pertaining to the exclusion of preferred embodiments. See id.
In Lupin, Judge Hamilton determined that she needed to construe the term in a
way that distinguishes it from the term “until substantially all of said drug is released,”
which was construed in that case to mean “at least 80% of the drug is released.” Lupin,
2011 WL 1877984, at *12. Based on the specification, the extrinsic evidence, and expert
testimony, Judge Hamilton adopted Depomed’s construction, noting that the evidence
supported a construction of “100% or something less than 100%.” Id. at *13. Judge
Hamilton, however, did not elaborate with respect to what “something less than 100%”
meant. See id.
The PTAB declined to adopt Depomed’s construction for this term, and instead
construed the term according to its plain, ordinary meaning:
The plain meaning of “until all of said drug is released” is
evident. If we were to adopt Patent Owner’s argument that
“all” can mean “less than all,” we would be ignoring the plain
meaning of the term. Moreover, although Patent Owner is
correct that certain other embodiments in the Specification
plateau at less than 100% of drug release, we note that certain
embodiments do plateau at 100%. See [‘475 Pat.], Fig. 1
(curve marked by filled diamonds); see also August Tech.
Corp. v. Camtek, Ltd., 655 F.3d 1278, 1285 (Fed. Cir. 2011)
(“The mere fact that there is an alternative embodiment
disclosed in the [asserted patent] that is not encompassed by
[our] claim construction does not outweigh the language of the
claim, especially when [our] construction is supported by the
intrinsic evidence.” (citation omitted)).
Furthermore, as noted above, we have determined that, as
properly construed, the phrase “releases substantially all” in
claim 43 means “at least 80% of the drug has been released.”
If we were to interpret “all” to mean the point at which the drug
37
release profile plateaus—even if less than 80%—then it would
be possible for a dosage form to release “all” of a drug, but not
“substantially all” of the drug. Such an inconsistency within
the claim would not be a reasonable construction of the term
“all.” Accordingly, we decline to construe “until all of said
drug is released” as broadly as Patent Owner requests and,
instead, construe it according to its plain, ordinary meaning.
(Dkt. 132-14 at 9-10.)
Here, Depomed raises the same or similar arguments it made in these prior
proceedings. Depomed acknowledges that its proposed construction diverts from the
plain and ordinary meaning of the term “all,” and argues that the term has a “special
meaning” in the context of the patents-in-suit. According to Depomed, the release of
“all” of said drug means the time when the plateau of the dissolution profile has been
reached, which may be at a point when less than 100% of the drug is released.
Depomed’s expert, Dr. Appel, explains that:
In sustained release dosage forms there is often some drug that
doesn’t exit the dosage form within a relevant time frame
(duration of dissolution test or time it takes to transit the entire
GI tract). Formulation scientists therefore look at the plateau
of the dissolution profile as representing all the drug that will
be released in a relevant time frame. There was not an
expectation that all sustained release formulations release
100% of the drug contained in them now or at the time of the
filing of the patents in 1997.
(Dkt. 132-17 at 20-21.) Stated differently, the dissolution profile is the point when all of
the drug that is going to be released, is released, which may be at an amount less than
100%.
38
To support its position, Depomed points to Example 1 of the patents-in-suit.
Example 1, supported by Figure 1 (reproduced below), shows three dosage forms, only
one of which releases 100% of the incorporated drug after nine hours.
‘475 Pat., Fig. 1. The other two dosage forms plateau in the same timeframe at a release
point of 90% of the incorporated drug. According to Depomed, all of these examples
would be viewed by the POSA as constituting “all of the drug” being released.
Depomed also relies on two FDA guidance documents.21 Dr. Appel summarizes
those documents as follows:
[T]he FDA Dissolution Guidance explains that there should be
a minimum of three time points for a dissolution study: “early,
middle and late,” the last of which “should be the time point
where at least 80% of drug has dissolved,” and “[if] the
maximum amount dissolved is less than 80%, the last point
should be the time when the plateau of the dissolution profile
has been reached.”
21
The FDA documents are: (1) Food and Drug Administration, Guidance for Industry:
SUPAC-MR: Modified Release Solid Dosage Forms (1997) (dkt 132-15); and (2) Food and
Drug Administration, Guidance for Industry: Extended Release Oral Dosage Forms:
Development, Evaluation, and Application of In Vitro/In Vivo Correlations (1997) (dkt. 132-16).
39
Similarly, the FDA SUPAC Guidance explains that the
endpoint of dissolution testing should occur “until either 80%
of the drug from the drug product is released or an asymptote
is reached.”
Both of the FDA guidances illustrate that it is not
expected that all of the drug is released in sustained release
dosage forms and therefore the plateau or asymptote of the
dissolution profile is taken as showing the release of all the
drug that is going to be released within a relevant time frame.
(Dkt. 132-17 at 21 (citations omitted).) It is therefore Depomed’s position that these
guidances support its construction and the understanding of the POSA that the term “all”
would cover something less than 100% in this context. Finally, as it did in the previous
cases, Depomed argues that a construction requiring 100% release would read out the
preferred embodiments where less than 100% of the drug is released. The Court notes
that while Depomed argues that all means less than 100%, it does not provide a floor or a
range for the meaning of the term.
Purdue contends that “all of said drug” should be given its plain and ordinary
meaning of 100%. Purdue argues that the POSA’s understanding of the term would not
have differed from how the term is generally understood. On this point, Purdue offers
three dictionary definitions, each defining the word “all” as an “entire” or “total” amount,
and the testimony of Dr. Atwood. (See dkt. 133-1 at 7.)22 Depomed, however,
22
American Heritage Dictionary (2d. ed. 1985) (defining “all” as “[t]he entire or total
number, amount, or quantity of”) (dkt. 133-5 at 83-86); Webster’s II: New College Dictionary
(1995) (defining “all” as “[t]he whole number, amount, or quantity of”) (dkt. 133-5 at 88-90);
Webster’s Ninth New Collegiate Dictionary (1989) (defining “all” as “the whole amount or
quantity of”) (dkt. 133-5 at 92-95).
40
characterizes Purdue’s reliance on these dictionaries as improper because they are
general-purpose dictionaries that predate the priority dates of the patents.
Purdue also makes multiple arguments based on intrinsic evidence. Focusing on
the language of claim 1 of the ‘475 Patent, Purdue states that the “drug” is first defined in
that claim as the “drug dispersed [in the solid polymeric matrix] at a weight ratio of drug
to polymer of from about 15:85 to about 80:20.” See n. 8, supra. Purdue contends that
this language refers to the amount of drug present in the claimed controlled release
dosage form, and that therefore “all of said drug” is all of the drug present in that
formulation. (See dkt. 133 at 11-12.) Purdue also notes that the term “all” is consistently
used throughout the patents-in-suit to mean 100%. See ‘475 Pat., cover page (“all of” the
inventors reside in California); col. 3, l. 37 (“all of these variations”); col. 4, l. 32 (“all of
these drugs”).
With respect to the examples provided in the written description, Purdue
acknowledges that some examples show less than 100% release of the drug, but argues
that the patents-in-suit also provide multiple examples showing 100% release of the drug.
See id., Figs. 1, 3, and 4. Purdue argues that in these examples the amount of drug
released is reported based on either actual or theoretical loading of drug in the
formulation, not when the drug hits a plateau, which suggests that the important metric is
the percentage of drug released relative to 100% drug loading.
With the testimony of Dr. Atwood, Purdue argues that the “goals” of the invention
(i.e., extending the time of delivery into the stomach and confining delivery and
absorption of the drug to the upper GI tract) support a construction requiring “all” or
41
100% of said drug. Dr. Atwood declares that “[i]f less than 100% of the drug was
released [] before the dosage form deteriorated so that it was no longer substantially
intact, the dosage form would leave the stomach. Thus the remaining drug release would
not be confined to the stomach and upper intestine.” (Dkt. 133-1 at 10.) In addition, Dr.
Atwood explains that “[r]eleasing all of the drug while the dosage form remains
substantially intact allows the claimed dosage form to avoid [transient overdose];
retaining some of the drug in the dosage form until the time when the dosage form
disintegrates might lead to transient overdose.” (Id.)
Purdue further contends that Depomed’s proposed construction creates
ambiguities and inconsistencies. Purdue contends that Depomed fails to adequately
articulate what is meant by the “plateau of the dissolution profile.” Dr. Atwood declares
that the POSA would not understand a plateau in drug release to necessarily mean that
“all” of the drug has been released from the formulation, or even that release of drug
from the formulation is complete. He explains that “formulations may exhibit pulsatile
release, characterized by a plateau followed by a period of rapid drug release.” (Id. at
11.)23 He also explains that artificial plateaus may be exhibited under certain conditions:
[I]f sink conditions do not exist in the dissolution test, the drug
release might artificially plateau due to the lack of
concentration gradient to drive drug release. Sink conditions
exist when the volume of dissolution media is at least three
times greater than the volume at the saturation point of the drug
contained in the drug delivery system being tested. If the drug
concentration in the surrounding dissolution media is
23
On this point, Dr. Atwood cited Singh, D.K., International Journal of Current
Pharmaceutical Review and Research, V. 2:2, May-July 2011. (Dkt. 133-2 at 80-106.)
42
saturated, the dissolution profile will plateau, even if there is a
significant amount of drug left in the dosage form.
(Dkt. 133-1 at 11 (citation omitted).)24 Depomed attacks these positions as irrelevant,
arguing that the patents-in-suit do not concern pulsatile release. (See dkt. 161 at 39-40.)
Finally, Purdue argues that Depomed’s construction for this term and its
construction for “substantially all of said drug” would lead to the inconsistent situation
identified by the PTAB where a dosage form could release “all” of a drug, but not
“substantially all” of the drug, if a plateau occurs at less than 80%.
The Court has considered the parties’ respective arguments and the relevant
evidence. The Court adopts Purdue’s proposed construction and construes the claim term
“until all of said drug is released” to mean “[until] 100% of the drug has been released.”
“[T]he words of a claim ‘are generally given their ordinary and customary
meaning.’” Phillips, 415 F.3d at 1312 (quoting Vitronics Corp. v. Conceptronic, Inc., 90
F.3d 1576, 1582 (Fed. Cir. 1996)). The “ordinary and customary meaning” is “the
meaning that the term would have to a person of ordinary skill in the art in question at the
time of the invention.” Id. at 1313. “Properly viewed, the ‘ordinary meaning’ of a claim
term is its meaning to the ordinary artisan after reading the entire patent.” Id. at 1321.
The Court finds that “all” in the context of the claims means “all” or “100%.” The
Court agrees with Judge Pisano that there is little intrinsic evidence to assist the Court in
determining what meaning the patentees intended for “all of said drug.” The patentees
24
On this point, Dr. Atwood cited Vaghela, B., et al., Journal of Applied Pharmaceutical
Science 01 (03); 2011: 50-56. (Dkt. 133-2 at 108-114.)
43
did not act as their own lexicographer with respect to this term, as they chose to with
other terms. See Thorner v. Sony Computer Entm’t Am. LLC, 669 F.3d 1362, 1365
(Fed. Cir. 2012) (“To act as its own lexicographer, a patentee must clearly set forth a
definition of the disputed claim term other than its plain and ordinary meaning.”
(quotations omitted)). The examples in the written description relied on by Depomed do
show the release of a drug at less than 100% for some dosage forms. However, a claim
need not cover every disclosed embodiment in the specification. See August Tech. Corp.
v. Camtek, Ltd., 655 F.3d 1278, 1285 (Fed. Cir. 2011) (“The mere fact that there is an
alternative embodiment disclosed in the [asserted patent] that is not encompassed by
[our] claim construction does not outweigh the language of the claim, especially when the
court's construction is supported by the intrinsic evidence.” (citation and internal
quotation marks omitted)); see also Baran v. Medical Device Techs., Inc., 616 F.3d 1309,
1316 (Fed. Cir. 2010) (“It is not necessary that each claim read on every embodiment.”).
The examples clearly include dosage forms that do indeed release 100% of the drug. See,
e.g., ‘475 Pat., Fig. 1.
As the PTAB correctly noted, Depomed’s proposed construction creates an
irreconcilable inconsistency between this term and the term “substantially all of said
drug,” as we construe it below. If this Court were to interpret “all” to mean the point at
which the drug release profile plateaus, a dosage form that plateaus at 50% release would
fall within the bounds of “all”, but not within the bounds of “substantially all.” Similarly,
a dosage form that plateaus at 80% release would fall within the bounds of both “all” and
“substantially all.” The claim term “substantially all” most certainly must be less than
44
“all.” Such an inconsistent situation persuades this Court that the plain, ordinary
meaning should control.
Accordingly, the Court construes the claim term “until all of said drug is released”
to mean “[until] 100% of the drug has been released.”
4.
Claim terms concerning swelling upon imbibition of water or
gastric fluid
For the claim terms concerning swelling upon imbibition of water or gastric fluid,
the dispute between the parties concerns two issues: (1) whether the construction should
include a specific size that the polymeric matrix must swell to in order to promote
retention in the stomach; and (2) whether the construction should include a specific
amount of time that matrix must remain in the stomach. Depomed’s proposed
constructions do not include specific dimensions or time amounts. Purdue’s proposed
constructions, on the other hand, do.
With respect to the “size” issue, Depomed argues that the intrinsic and extrinsic
evidence supports its constructions. First, Depomed argues that the written description
never limits the swollen polymeric matrix to a minimum size. Depomed contends that
the swollen size is discussed in only functional terms, which counsels against construing
the terms to include specific dimensions of the swollen tablet. See id., col. 5, l. 66 – col.
6, l. 3 (the matrix “swells upon ingestion, preferably to a size that is at least about twice
its unswelled volume, and that promotes gastric retention during the fed mode”); col. 6,
ll. 19-21 (“the tablet swells to a size large enough to cause it to be retained in the stomach
during the fed mode”); col. 9, ll. 1-5 (the matrices “swell in size . . . to achieve a size that
45
will be retained in the stomach when introduced during the fed mode”). The only
specific dimensions that are provided in the written description are of tablets in
unswollen states, which range in size from 3mm to 22mm. See id., col 10, ll. 20-39; col.
13, ll. 27-33; col. 14, ll. 6-36, 48-50; col. 14, l. 61 – col. 15, l. 40; col. 15, ll. 51-59; col.
16, ll. 3-31, 54-57; col. 17, ll. 14, 35-36.25 Depomed argues that if the smaller of these
tablets (i.e., the 3 mm and 4 mm tablets) were to swell to the preferred at least about
twice unswelled volume, these swollen tablets would still fall short of the 9.5 mm
dimensions sought by Purdue. Depomed also argues that the phrase “when swollen in a
dimensionally unrestricted manner,” found in the claims of the ‘280 Patent, should be
given its plain, ordinary meaning,26 and should not be limited to at least two directions.
Depomed’s expert, Dr. Appel, opines that a pharmaceutical formulation may not
need to swell to the size suggested by Purdue to promote retention in the stomach during
the fed mode. (See dkt. 132-17 at 14.) Dr. Appel declares that in 1997, the POSA
understood that there was no per se cutoff for gastric retention. (Id.)27 Dr. Appel also
25
The written description notes that these “shapes and sizes can be varied considerably.”
Id., col. 10, ll. 38-39.
26
Depomed’s expert, Dr. Appel, declares that the POSA would understand the plain,
ordinary meaning of “when swollen in a dimensionally unrestricted manner” to be “that swelling
of the dimensions of the dosage form [do] not have any restriction.” (Dkt. 132-17 at 13.)
27
Dr. Appel cites C, Timmermans J. Moes A.J., The cutoff size for gastric emptying of
dosage forms, J. Pharm. Sci. 82, 8:854 (1993), which states that “there is no exact cutoff size per
se but a gradation of sizes over which predictable emptying from a fed stomach becomes
uncertain and highly variable.”
46
references excerpts of a 1989 book chapter,28 cited by Purdue, stating that particles above
4 mm may be passed not at all or only slowly from the food filled stomach.” (Id.)29
Purdue argues that the size of the particles must logically be tied to the size of the
pylorus. The written description explains that in order to retain particles in the stomach,
the particles must swell to a size greater than that of the pylorus. ‘475 Pat., col. 11, l. 65
– col. 12, l. 4. (“Indigestible particles greater than the size of the pylorus are retropelled
and retained in the stomach. Particles exceeding about 1 cm in size are thus retained in
the stomach for approximately 4 to 6 hours. The dosage form of the present invention is
designed to achieve the minimal size through swelling . . . .”).
Purdue’s expert, Dr. Atwood, declares that to be greater than the size of the
pylorus, a formulation must swell in at least two directions. (See dkt. 133-1 at 24-25.)
To support his position, Dr. Atwood cites the use of the term “dimensionally unrestricted
manner” in the patents-in-suit and the size descriptions of the unswollen tablets given in
multiple dimensions. Dr. Atwood also states that swelling in at least two dimensions is
important to achieving gastric retention, and that a POSA “would understand that a
dosage form that is longer than the pyloric sphincter but whose diameter is less than the
pylorus may not be retained; it could exit through the pylorus when its long axis pointed
28
Hardy, et al., Drug delivery to the gastrointestinal tract, Wilson. Ellis Horwood
Limited, 1989.
29
The excerpt from Hardy states: “[P]ostcibal gastric transit of particles is characterized
by high discrimination so that particles of food mostly 1 mm or less are emptied; a size which is
readily digestible. Similarly particles of drug or plastic at or below this size are rapidly passed.
Particles 1-3mm in diameter are passed more and more slowly as the size increases over this
range, and particles above 4 mm may be passed not at all or only slowly from the food filled
stomach.” (Dkt. 132-19 at 6.)
47
directly at the pylorus.” (Dkt. 133-1 at 24.) Dr. Atwood opines that a POSA would
understand 1 cm to mean not less than 9.5 x 9.5 mm. (Id.) He states that despite
conflicting reports in the literature at the time of the invention concerning the size of
dosage forms that are retained in the stomach, it was recognized that objects less than 8
mm are not reliably retained in the stomach during the fed mode, and that between 7-10
mm there is a gradation of size over which predictable emptying from the fed stomach
becomes uncertain and highly variable. (Id.)30 Dr. Atwood concludes that given this
information, a POSA would have been taught away from using formulations less than
10mm. (Id. at 25.)
Purdue also argues that Depomed disclaimed embodiments that only swell in one
dimension during the IPR proceedings.31 Depomed refutes this point, and argues that its
30
On this point, Dr. Atwood relies on the Declaration of Dr. Hopfenberg submitted on
behalf of Depomed in the Ivax case, which cited Khosla et al., Gastrointestinal Transit of NonDisintegrating Tablets in Fed Subjects, Int’l J. for Pharmaceutics 53, 107-117 (1989) and Jacques
Timmermans & Andre J. Moes, The Cutoff Size for Gastric Emptying of Dosage Forms, J.
Pharm. Sci., 82, 854 (1993). (See dkt. 133-3 at 54-98.)
31
In its Preliminary Response to the Petition for Inter Partes Review of U.S. Patent No.
6,340,475, Depomed attacked a prior art reference asserted by Purdue as follows:
Even if the data on dosage forms containing alprenolol HCL
(lacking the requisite solubility) set forth in the Park report is
analyzed, it is clear that the data do not satisfy swelling to a size
sufficient to promote retention in the stomach in the fed mode.
Claim 1 recites that the polymeric matrix is one that swells to attain
a size large enough to promote retention in the stomach during said
fed mode. The data in the Park report tabulate the swelling
parameters of the dosage form only in terms of a single dimension
– the diameter – and states that Park’s tests confirm Baveja’s
formulations swell to about 13.5 – 14.5 mm. Purdue provides no
information regarding the thickness of the dosage form. It is
conceivable that the tablets disclosed by Baveja and reproduced for
the data in the Park report would not provide the necessary swelling
48
statements during the IPR proceedings do not operate as a clear disavowal of claim
scope. Depomed asserts that it was attacking Purdue’s expert’s (Park) unreliable
methodologies and failure to disclose the thickness dimension of the reproduced tablets.
With respect to the “time” issue, Depomed argues that the intrinsic evidence
supports its construction. Depomed points to the abstract, which does not give a specific
time amount that the swollen matrix must remain in the gastric cavity. Instead, the
abstract states that the dosage form is retained for “several hours.” See ‘475 Pat.,
abstract. Depomed also points to a portion of the Summary section that discusses the
objectives of the polymeric matrix; one being to retard the rate of diffusion of a drug to
provide multi-hour, controlled delivery in the stomach. See id., col. 6, ll. 18-24.
Depomed acknowledges that the written description states that “particles exceeding about
1 cm in size are thus retained in the stomach for approximately 4 to 6 hours,” id, col. 11,
l. 67 – col. 12, l. 2, but argues this is a single embodiment that should not be read into the
claims. Depomed argues that Purdue’s construction would exclude the embodiments
illustrated in Examples 1, 4, and 6, that each show a formulation that releases 90% or
more of a drug in less than 4 hours.
Purdue argues that the term “remains in the stomach for several hours” must be
confined to a specific time period. Purdue argues that the written description explains
that the fed mode typically lasts only 4 to 6 hours, and thus the “several hours” refers to
in their thickness dimension to be of a size large enough to promote
retention in the stomach in the fed mode.
(Dkt. 133-5 at 184.)
49
the length of time of the fed mode. See ‘475 Pat., col. 2, ll. 19-20 (“the duration of the
fed mode . . . typically lasts for only 4 to 6 hours”). Purdue also argues that the written
description consistently describes the length of time that the formulation remains in the
stomach as at least four hours. See id., col. 3, ll. 3-7 (“The swellable hydrophilic matrix
of the present invention protects the yet undelivered drug during the 4 to 6 hour delivery
period during which the drug is continuously released while the dosage form is retained
in the stomach.”); col. 11, l. 67 – col. 12, l. 2 (“Particles exceeding about 1 cm in size are
thus retained in the stomach for approximately 4 to 6 hours.”); col. 17, ll. 19-21 (“In the
fed trials, the tablets demonstrated multiple-hour retention in the stomach in all subjects,
80% of the contents of all tablets being retained at 4 hours.”). Purdue contends that these
discussions are more relevant than the general disclosures that Depomed relies on. With
respect to example 1 (showing release of 90% or more of a drug in less than 4 hours),
Purdue contends that this example should not be considered because it does not discuss
retention in the stomach.
The Court has considered the parties’ respective arguments and the relevant
extrinsic evidence. For the following reasons, the Court adopts Depomed’s proposed
constructions.
The claims themselves do not provide specific swollen dimensions for a dosage
form. Instead, as Depomed correctly points out, the patentees chose to claim the size
functionally. See, e.g., ‘475 Pat., col. 17, ll. 52-53 (“attaining a size large enough to
promote retention in the stomach during said fed mode.”). Similarly, the written
50
description does not provide specific swollen dimensions for the dosage forms. The
discussion regarding the pylorus and particle size is also far from conclusive:
Indigestible particles greater than the size of the pylorus are
retropelled and retained in the stomach. Particles exceeding
about 1 cm in size are thus retained in the stomach for
approximately 4 to 6 hours. The dosage form of the present
invention is designed to achieve the minimal size through
swelling following ingestion during the fed mode.
Id., col. 11, l. 65 – col. 12, l. 4. The Court does not view this passage as setting a limit to
the particle size sufficient to be retained in the stomach. The patents-in-suit do not
articulate a size, or range of sizes, for the pylorus. They merely state that particles larger
than that part of the stomach will be retained. It is clear that particles exceeding about 1
cm in size will be retained, however the use of the word “about” suggests that something
less may also be retained. The final sentence referring to “the minimal size” is partly
unclear. The term “minimal size” is not defined in the patents-in-suit. This sentence
could refer to “about 1 cm” or it could generally refer to the minimal size needed for
retention in the stomach.
Purdue’s construction cannot be correct. As discussed above, the written
description does provide dimensions for unswollen tablets. If certain of these tablets
were to swell to their preferable size that is at least about twice its unswelled volume,
their dimensions would fall short of the 9.5 mm x 9.5 mm limitation proposed by Purdue.
Adopting Purdue’s construction would therefore exclude preferred embodiments. Adams
Respiratory Therapeutics, Inc. v. Perrigo Co., 616 F.3d 1283, 1290 (Fed. Cir. 2010) (“A
claim construction that excludes [a] preferred embodiment ‘is rarely, if ever, correct and
51
would require highly persuasive evidentiary support.’” (quoting Vitronics Corp. v.
Conceptronic Inc., 90 F.3d 1576, 1583-84 (Fed. Cir. 1996)).
The Court appreciates Purdue’s argument that swelling in more than one
dimension can be important to achieving gastric retention. However, we do not read
Depomed’s statements to the PTAB as amounting to a clear and unmistakable disclaimer
of swelling in only one direction. See 3M Innovative Props. Co. v. Tredegar Corp., 725
F.3d 1315, 1325 (Fed. Cir. 2013) (“[I]n order for prosecution disclaimer to attach, the
disavowal must be both clear and unmistakable.”). Where the alleged disavowal is
ambiguous, or even amenable to multiple reasonable interpretations, the Federal Circuit
has counseled against finding disclaimer. See Avid Tech., Inc. v. Harmonic, Inc., 812
F.3d 1040, 1045 (Fed. Cir. 2016). Depomed’s statements to the PTAB can reasonably be
interpreted as arguing that Purdue had not met its burden because the reference was
unclear as to whether the tablet would be retained in the stomach. Accordingly, we do
not find disclaimer that would require us to construe the claim term to include two
dimensions. We note that even if we did find disclaimer, we would not adopt the
dimensions set forth by Purdue for the reasons stated above. We also decline to replace
the dimensions proposed by Purdue with dimensions of our own choosing. We believe
such an act would be improper. As Judge Breyer noted in the Ivax case, “[a] patentee has
the right to claim the invention in terms that would be understood by persons of skill in
the art, and “mathematical precision should not be imposed for its own sake.” Ivax, 2006
WL 3782829, at *13 (citation omitted).
52
In addition, for the reasons stated above, we also find that the phrase “when
swollen in a dimensionally unrestricted manner,” found in the claims of the ‘280 Patent,
should be given its plain, ordinary meaning and should not be limited to at least two
directions. Nothing in the intrinsic or extrinsic evidence requires us to import such a
limitation.
With respect to the “time” issue, we decline to adopt the limitations proposed by
Purdue. The intrinsic evidence supports our construction. The claim terms at issue do
not include a specific time limitation. They each state that swelling promotes “retention
in the stomach during said fed mode.” See, e.g., ‘475 Pat., col. 17, ll. 52-53 (emphasis
added). We agree with Purdue that the written description states that the fed mode
“typically lasts for only 4 to 6 hours,” however, nothing in the claims requires the dosage
form to remain in the stomach for the entirety of the fed mode. Other language found in
the written description also counsels against drawing an artificial line at 4 hours. See,
e.g., id., col. 11, l. 67 – col. 12, l. 2 (“Particles exceeding about 1 cm in size are thus
retained in the stomach for approximately 4 to 6 hours.” (emphasis added)). The use of
the term “approximately” in this context is evidence that the patentees did not intend to
put forth a limitation requiring the dosage form to remain in the stomach for at least 4
hours.
Accordingly, we construe the term “said polymeric matrix being one the swells
upon imbibition of water thereby attaining a size large enough to promote retention in the
stomach during said fed mode” and “said polymeric matrix being one that swells upon
imbibition of gastric fluid to a size large enough to promote retention in the stomach
53
during said fed mode” to mean “the dosage form, which comprises a polymeric matrix,
increases in size due to the ingress of [water/gastric fluid], such that when the dosage
form is introduced into the stomach in the fed mode, the dosage form remains in the
stomach for several hours.” With respect to the claim term “when swollen in a
dimensionally unrestricted manner as a result of imbibition of [water/gastric fluid] is of a
size exceeding the pyloric diameter in the fed mode to promote retention in the stomach
during said fed mode” found in claims 1 and 43 of the ’280 Patent, we construe the
former part of that term, “when swollen in a dimensionally unrestricted manner as a
result of imbibition of [water/gastric fluid],” to have its plain, ordinary meaning. We
construe the latter part, “is of a size exceeding the pyloric diameter in the fed mode to
promote retention in the stomach during said fed mode,” to mean “such that when the
dosage form is introduced into the stomach in the fed mode, the dosage form remains in
the stomach for several hours.”
5.
Claim terms concerning “substantially all of said drug”
Purdue has not proposed a construction for the terms including the phrase
“substantially all of said drug.” Instead, Purdue maintains that these claim terms are
indefinite.
As discussed above, some of these claim terms have been construed by three other
district courts.32 However, those courts were not asked to consider the question of
32
One of the three district courts simply accepted the construction agreed to by the
parties. See Section I.B.5, supra.
54
indefiniteness. In Ivax, the parties’ dispute over the term “substantially all” was purely
quantitative. Depomed sought a construction of “about 80%” and Ivax sought a
construction of “at least 90%.” See Ivax, 2006 WL 3782829, at *4. Both parties argued
that the intrinsic evidence, specifically the examples illustrating drug release, supported
their respective positions. See id. Judge Breyer found the parties’ competing contentions
to be reasonable, but found the intrinsic evidence to be an “inadequate basis for a
definitive construction of the disputed term.” Id. As a result, Judge Breyer turned to the
extrinsic evidence, specifically the FDA Guidance documents, and adopted Depomed’s
proposed construction. Id. at *5 (“In the absence of any strong indication in the intrinsic
record as to the boundary of the vague and approximate term ‘substantially all,’ the
extrinsic FDA source offers the clearest insight into the understanding that one of skill in
the art would have of the term.”).
In Sun, the parties’ dispute was again quantitative in a sense. Sun argued that the
plain, ordinary meaning of “about 100%” should apply, and Depomed maintained its
position that the proper construction was “at least 80%.” See Sun, 2012 WL 3201962, at
*10. Judge Pisano expressed the same apprehension toward the intrinsic evidence as
Judge Breyer, see id., at *11 (noting that the examples “reveal wide, varying release rates
at the eight hour mark, thereby making the meaning of ‘substantially all’ unclear” and
“[a]t the very least, the specification demonstrates that the patent applicants meant
something other than ‘about 100%’”), and agreed with and deferred to Judge Breyer’s
reliance on the FDA Guidance documents in adopting Depomed’s construction.
55
Purdue acknowledges the previous construction history of these terms, but argues
that the standard for proving indefiniteness is now less demanding after the Supreme
Court’s decision in Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120 (2014). In
Nautilus, the Supreme Court rejected the Federal Circuit’s “unsolubly ambiguous”
standard for indefiniteness. See id. at 2124. The Court held that “a patent is invalid for
indefiniteness if its claims, read in light of the specification delineating the patent and
prosecution history, fail to inform, with reasonable certainty, those skilled in the art about
the scope of the invention.” Id. Following Nautilus, the Federal Circuit reiterated that
“general principles of claim construction apply” to the question of indefiniteness. Biosig
Instruments, Inc. v. Nautilus, Inc., 783 F.3d 1374, 1377 (Fed. Cir. 2015) (internal
quotation marks omitted). The Federal Circuit also explained that, in its view, Nautilus
did not imply that terms of degree are inherently indefinite. Id. at 1378. Terms of degree
are definite when they provide “enough certainty to one of skill in the art when read in
the context of the invention.” Id. (citation omitted).
Purdue argues that the intrinsic evidence fails to inform, with reasonable certainty,
the meaning of the phrase “substantially all of said drug.” Purdue contends that the claim
language itself is vague, and that the specification does not provide an express definition
for the term “substantially all.” (See dkt. 133 at 17-20.) Purdue describes Depomed’s “at
least 80%” construction as a “completely arbitrary selection unsupported by the intrinsic
record,” and argues that because the examples and figures exhibit widely-varying release
percentages, a POSA would not be reasonably certain when “substantially all” of the drug
has been released. (See id. at 20.) Purdue further argues that the patentees were capable
56
of using more precise language than the ambiguous “substantially all” language, as
evidenced by the patentees’ choice to describe the amount of drug retained as “at least
about” a certain percentage. (See id. at 21-22.)
Purdue contends that the extrinsic evidence, namely the FDA Guidances, does not
save Depomed’s claims from being indefinite. Purdue argues that nothing in the intrinsic
record suggests that a POSA would focus on these specific FDA Guidances. (See id. at
23-24.) Purdue notes that the FDA Guidances never use the phrases “all of” or
“substantially all of” to describe drug release and were not published until after the
effective filing date of the patents-in-suit. (Id. at 24.)
Purdue also argues that the FDA Guidances deal with a different issue from the
patents-in-suit. (See id.) Purdue’s expert, Dr. Atwood, declares that the FDA Guidances
“relate to dissolution testing for a very specific purpose: determining how similar the
release profiles are between two formulations.” (Dkt. 133-1 at 17.) He opines that the
FDA Guidances “do not provide general guidance for dissolution testing or otherwise
relate to a determination of whether substantially all of the drug has been released from a
formulation.” (Id.) He states that these documents provide “recommendation[s] for
sampling times,” in particular “a minimum of three time points covering the ‘early,
middle, and late stage of the dissolution profile.’” (Id. at 19 (citation omitted).) He
explains that the last point “is recommended to be where at least 80% of the drug has
dissolved, unless the maximum amount dissolved is less than 80%, where the last time
point should be when the plateau of the dissolution profile is reached.” (Id.) He further
argues that the 80% mark has nothing to do with the meaning of the term “substantially
57
all of the drug” because the 80% point was chosen by the FDA “[i]n order to prevent
results skewed toward a finding of similarity” because “formulations may have very
similar release profiles after 80% of the drug is released.” (Id. at 19-20.) Dr. Atwood
argues that the literature explains that it is generally best to characterize the entire release
profile. (Id. at 20.)33 He argues that when the literature discusses “essentially complete”
release, the literature does not use the 80% benchmark. (Id. at 20-21.)34 He further
argues that the 80% time point is a function of the way POSAs assess the lot-to-lot
quality of a drug product. (See id. at 21.)
33
On this point, Dr. Atwood cites P.J. Skelly et al., Report of Workship on In Vitro and
In Vivo Testing and Correlation for Oral Controlled/Modified-Release Dosage Forms, Journal of
Pharm. Sciences, September 1990, Vol. 79, No. 9, at 853, which states:
At a minimum, at least three time points are recommended, but more
are strongly encouraged: a 1-h time point to assure that there is no
dose dumping, a second time point around 50% dissolution, and a
third time point around 80% dissolution. However, generally, it is
best to characterize the entire in vitro release profile.
(Dkt. 133-3 at 42.)
34
Dr. Atwood relies on USP 23 § 1088, In Vitro and In Vivo Evaluation of Dosage
Forms (1995), which states:
At least three test times are chosen to characterize the in vitro drug
release profile for pharmacopeial purposes. Additional sampling
times may be required for drug approval purposes. An early time
point, usually 1 to 2 hours, is chosen to show that potential dose
dumping is not probable. An intermediate time point is chosen to
define the in vitro release profile of the dosage form, and a final time
point is chosen to show essentially complete release of the drug.
Test times and specifications are usually established on the basis of
an evaluation of drug release profile data.
(Id. at 48.)
58
Purdue also argues that the POSAs did not consider only the 80% release rate in
evaluating dissolution profiles. Purdue argues that a 90% release rate was both
considered and employed prior to the publication of the FDA Guidances. (See id. at 2324.)35
Depomed disagrees with Purdue’s position that the “substantially all” claim terms
are indefinite under the standard announced in Nautilus. Depomed argues that Purdue’s
evidence fails to demonstrate that the claim terms are not reasonably capable of being
construed and understood by a POSA, and attacks Purdue’s positions as devoid of proper
context. (See dkt. 132 at 26-28.) Depomed stresses that the prior history regarding the
construction of these terms, i.e., by multiple district courts, the PTAB, and many experts,
demonstrates that these claim terms are capable of construction and are not indefinite.
(See id. at 26-27.)
Depomed argues that its construction for this term is supported by the intrinsic
evidence, pointing to a statement in the Summary section referring to a “majority of the
drug” being released, and multiple examples that show at least 80% of the drug being
released within ten hours. See ‘475 Pat., col. 6, ll. 10-15; col. 12, l. 10 – col. 13, l. 8; col.
13, l. 65 – col. 14, l. 50; col. 15, ll. 43-60; Figs. 1, 4, 5, and 7.
35
Purdue cites FDA Approval Package for NDA 20-616/S-001 (July 29, 2007) (Dkt.
133-3 at 32) and International Patent Publication No. WO 92/04013 (Dkt. 133-5 at 140-158.)
59
Depomed’s expert, Dr. Appel, opines that these examples are significant due to the
plateaus in the dissolution profile during the later stages of drug release in sustained or
extended release dosage forms:
Many sustained or extended release dosage forms show a
plateau in the dissolution profile during the later stages of
release. This plateau is expected with certain types of dosage
forms that release via mechanisms that provide a smaller
driving force for drug release at later portions of the release
profile, e.g. diffusional hydrophilic matrix tablets and osmotic
tablets.
The rate of drug release from [] hydrophilic matrix tablets that
release via a diffusional mechanism is proportional to the
difference between the concentration of drug in solution inside
the dosage form and outside the dosage form. During much of
the release profile the drug concentration in the dosage form is
saturated (at the solubility of the drug in the specific
environment of the tablet). At the later stages of the release
profile, the drug is depleted so that concentration of drug inside
the tablet falls below the saturated solubility. This results in a
decrease in the driving force for release and a lower release
rate. This effect continues until there is effectively no driving
force for drug release and can result in a significant plateau for
drug release, a phenomenon referred to as “tailing.” This is
nicely illustrated in Figure 1 of the ‘475 Patent that shows
tailing occurring in the release profile between 70-90% release.
Therefore, in light of the disclosure in the patents, it is
appropriate to say that “substantially all” of the drug is released
once 80% of the drug has been released.
(Dkt. 132-17 at 17.)
Depomed, citing the two FDA Guidance documents, argues that the extrinsic
evidence supports its constructions. Depomed argues that these documents explain that
in in vitro/in vivo dissolution testing, the endpoint of testing should occur where at least
80% of the drug from the drug product is dissolved. Depomed’s expert, Dr. Appel,
60
opines that based on these documents, in conjunction with the disclosures in the patentsin-suit, the POSA would understand the “substantially all of said drug” terms to mean “at
least 80% of the drug.” (See dkt. 132-17 at 18-19.) Dr. Appel explains that:
These FDA Guidance documents were written by and for those
skilled in the art, and therefore reflect the understanding of a
person of skill in the art of pharmaceutical dosage forms in
1997. A person of skill in the art in the pharmaceutical industry
would look for such FDA publications for guidance in the
meanings and scopes of relevant subject matters, over other
sources of information, since the FDA ultimately decides
whether to approve a new drug product. It is imperative that
the formulator understand the FDA’s guidances regarding
appropriate testing of dosage forms in development to ensure
the dosage for developed meets FDA standards.
(Id.)
The Court has considered the parties’ respective arguments and the relevant
evidence. The Court concludes that the claim terms including the phrase “substantially
all of said drug” are not indefinite. Accordingly, the Court will adopt the constructions
proposed by Depomed.
“[A] claim must ‘inform those skilled in the art about the scope of the invention
with reasonable certainty’ to meet the definiteness requirement of 35 U.S.C. § 112, ¶ 2.”
Liberty Ammunition, Inc. v. United States, 835 F.3d 1388, 1396 (Fed. Cir. 2016)
(quoting Nautilus, 134 S. Ct. at 2129). Yet, we must recognize that “absolute precision is
unattainable” when drafting patent claims. Nautilus, 134 S. Ct. at 2129. If absolute
precision were required, terms like “substantially” or “about” would have no place in
patent law. The term “substantially” is in fact common in general usage and patent claim
drafting, and its use alone is not enough to make a claim indefinite. See, e.g., Aventis
61
Pharm. Inc. v. Amino Chemicals Ltd., 715 F.3d 1363, 1377 (Fed. Cir. 2013) (construing
“substantially” as “largely but not wholly”). It is clear to this Court that “a patentee need
not define his invention with mathematical precision in order to comply with the
definiteness requirement.” Sonix Tech. Co. v. Publ’ns Int’l, Ltd., No. 2016-1449, 2017
WL 56321, at *5 (Fed. Cir. Jan. 5, 2017) (quoting Invitrogen Corp. v. Biocrest Mfg.,
L.P., 424 F.3d 1374, 1384 (Fed. Cir. 2005)).
We agree with Judge Breyer that “[c]ommon sense indicates that ‘substantially all’
of a substance refers to some percentage approaching 100% of the relevant material—in
other words, some measure just short of it.” Ivax, 2006 WL 3782829, at *4. While the
top boundary may be capable of a definition using merely words, the bottom boundary
here is what is difficult to define. We agree that the intrinsic record fails to provide a
strong indication as to the boundary of the term. See id. at *5. The term is not defined in
the claims or the specification. The statement in the Summary section referring to a
“majority of the drug” being released is less than helpful, as it could be interpreted to
mean greater than 50% and less than or equal to 100%. See U.S. Philips Corp. v. Iwasaki
Elec. Co., 505 F.3d 1371, 1379 (Fed. Cir. 2007). The multiple examples showing at least
80% of the drug being released within ten hours are only somewhat persuasive. Twothirds of the final drug release percentage measurements are above 80%, however there is
variance within those measurements. (See dkt. 133 at 20.) We, like the other district
courts before us, must turn to the extrinsic evidence to determine the meaning of this
claim.
62
The FDA Guidances are most helpful in our mission to determine if these claim
terms are indefinite. These documents were written to provide “recommendations to
pharmaceutical sponsors of new drug applications (NDAs), abbreviated new drug
applications (ANDAs), and abbreviated antibiotic drug applications (AADAs)” related to
the composition and manufacture of “a modified release solid oral dosage form during
the postapproval period,” (dkt. 132-15 at 6), and “pharmaceutical sponsors who intended
to develop documentation in support of an in vitro/in vivo correlation (IVIVC) for an oral
extended release (ER) drug product for submission in a [NDA], [ANDA], or [AADA].”
(Dkt. 132-16 at 5.) In other words, they were written for the POSA.
The data collected in the patents-in-suit appears consistent with the FDA
Guidances, that look to the “at least 80%” drug release as a reasonable marker of how
much drug is released in the “last stage of dissolution.” As discussed above, the FDA
Guidances explain that “[t]he last time point should be the time point where at least 80%
of drug has dissolved” or “[i]f the maximum amount dissolved is less than 80%, the last
time point should be the time when the plateau of the dissolution profile has been
reached.” (Dkt. 132-16 at 21, see also dkt. 132-15 at 11 (“Adequate sampling should be
performed, for example, at 1, 2, and 4 hours and every two hours thereafter until either
80% of the drug from the drug product is released or an asymptote is reached.”.) The
literature directed to the POSA places considerable emphasis on the 80% mark, as the
appropriate end point for testing dissolution of a drug. The Court finds these documents
to be highly persuasive evidence that the claim term “substantially all,” as read in light of
the specification delineating the patent and prosecution history, informs, with reasonable
63
certainty, those skilled in the art about the scope of the invention. Accordingly, we
conclude that the substantially all claim terms are not indefinite. We agree with and give
appropriate deference to Judge Breyer and Judge Pisano’s reliance on the FDA
Dissolution Guidance and will adopt Depomed’s proposed construction.
Accordingly, the Court construes the “substantially all” claim terms as follows:
“releases substantially all of said drug within about eight hours after such immersion”
means “at least 80% of the drug has been released after eight hours of immersion in
gastric fluid;” “releases substantially all of said drug after such immersion” means “at
least 80% of the drug has been released after immersion in gastric fluid;” “releases
substantially all of said drug within about ten hours after such immersion” means “at least
80% of the drug has been released after teen hours of immersion in gastric fluid;” “until
substantially all of said drug is released” means “at least 80% of the drug has been
released;” and “while releasing substantially all of said drug within said stomach where
said drug is maintained in an acidic environment” means “at least 80% of the drug has
been released after immersion in gastric fluid.”
6.
Claim terms concerning poly(ethylene oxide) molecular weights
With respect to these claim terms, Depomed contends that no construction is
necessary, and that the plain and ordinary meaning should apply because the POSA
would understand the plain and ordinary meaning of “about” to mean “approximately.”
Depomed’s expert, Dr. Appel, explains that polymer molecular weight is typically
measured by means of gel permeation chromatography (GPC). (See dkt. 132-17 at 2425.) According to Dr. Appel, “GPC is known by persons skilled in the art to have
64
accuracy and precision of 5-10% when calculating a molecular weight average, meaning
any value within 5-10% could represent the same underlying molecular weight
distribution.” (Id. at 4.) Dr. Appel cautions against assigning a fixed range to the word
“about” because the accuracy of polymer molecular weight measurements is highly
dependent on polymer type, sample preparation, measurement equipment, analytical
technique, and data analysis. (Id. at 25.) However, when considering the range offered
by Purdue, Dr. Appel does state that “a more appropriate range would be 20% variation,
making said range 3,600,000 to 12,000,000 and 4,000,000 to 9,600,000, respectively.”
(Id.) Depomed acknowledges that these ranges would overlap, but asserts that they still
claim different ranges, and, therefore, cover different inventions. (See dkt. 161 at 46-47.)
Purdue employs a significant figure analysis to arrive at its proposed constructions
for these terms. (See dkt. 133 at 31-32.) Purdue’s expert, Dr. Atwood, explains that
When reporting numerical values, it is important to properly
identify which numbers are significant—i.e., which numbers
are intended to be precise—as opposed to which numbers are
merely placeholders to indicate the scale of the number. The
rule recognized by those skilled in the art is that numbers that
are within the range of uncertainty are rounded. Thus, the last
reported significant figure can have a maximum uncertainty of
± 1.
(Dkt. 133-1 at 25-26.) Based on the significant figure analysis, Purdue states that
The number “4,500,000” has at least two significant figures,
the “4” and the “5.” (The zeros may or may not be significant,
depending on context.) Thus, “about 4,500,000” should not
extend below 4,400,000. Given that the patent contrasts
4,500,000 with 5,000,000, the first zero in “5,000,000” is also
significant, so “about 5,000,000” should not extend below
4,900,000.”
65
(Dkt. 133 at 32.) However, Dr. Atwood opines that the POSA would have understood
the maximum uncertainty of the claimed poly(ethylene oxide) molecular weights to be
5%. (Dkt. 133-1 at 26.) He states that an uncertainty of 6% or greater would result in a
scenario with overlapping ranges between the bounds of the claim terms. (See id.) Thus,
Purdue adopts 5% as the uncertainty and concludes that “about 4,500,000 to about
10,000,000” means 4,275,000 to 10,500,000 and “about 5,000,000 to about 8,000,000”
means “4,750,000 to 8,400,000.” (See dkt. 133 at 32.)
Finally, Purdue argues that a determination that these claim terms have their plain,
ordinary meaning would be inadequate to resolve the dispute between the parties, and
requests that this Court provide some definition of the metes and bounds of these claim
terms.
The Court has considered the parties’ respective arguments and the relevant
evidence. The Court construes the claim term “about 4,500,000 to about 10,000,000” to
mean “3,600,000 to 12,000,000”, and construes the claim term “about 5,000,000 to about
8,000,000” to mean “4,000,000 to 9,600,000.”
For the claim terms “about 4,500,000 to about 10,000,000” and “about 5,000,000
to about 8,000,000,” there is little, if any, intrinsic evidence sufficient to guide the
Court’s determination. The written description does not provide an explicit definition for
the term “about” in the context of these claims. The ranges of molecular weights of
preferred poly(ethylene oxide) polymers and more preferred poly(ethylene oxide)
polymers are merely reported in the written description without any further elaboration.
66
See ‘475 Pat., col. 8, ll. 31-40. In addition, neither party references any portion of the
prosecution history that may guide our analysis.
Both parties rely exclusively on the testimony of their respective experts. We find
the testimony of Dr. Appel to be more persuasive on this point. As discussed above, Dr.
Appel’s testimony explains that the accuracy of a molecular weight measurement is
highly dependent on multiple factors, and that the word “about,” in that context, must
refer to a range wider than the known accuracy of the measurement technique, which she
opines is 20%. The significant digit analysis put forth by Purdue is too imprecise.
Purdue and its expert fail to provide any explanation as to why certain digits, in the
context of a molecular weight range of a polymer, must be significant. In fact, Purdue
states that “[t]he zeros may or may not be significant, depending on context.” (Dkt. 133
at 32.) Purdue’s arguments in no way consider the realities of molecular weight
measurement. Moreover, Purdue argues that “about 4,500,000” should not extend below
4,400,000, yet advocates for a variance of 5% which results in a figure (4,275,000) that
does extend below 4,400,000. Purdue’s arguments related to the significant figure
analysis fail to persuade us.
The Court also does not find Purdue’s argument related to claim differentiation to
be persuasive. The Court recognizes that the claim terms, as construed, overlap in part.
However, they still claim different ranges of molecular weights and, therefore, are
different. See In re Rembrandt Techs., LP, 496 F. App’x 36, 45-46 (Fed. Cir. 2012).
The Court appreciates Purdue’s concern that given the parties’ dispute, declining
to construe this term or construing it to have its plain and ordinary meaning would be
67
inadequate. As a result, the Court will adopt the range set forth by Depomed in the
alternative. This construction accounts for the realities of molecular weight
measurement, and will provide a definition for the metes and bounds of the claims.
Accordingly, the Court construes the claim term “about 4,500,000 to about
10,000,000” to mean “3,600,000 to 12,000,000”, and construes the claim term “about
5,000,000 to about 8,000,000” to mean “4,000,000 to 9,600,000.”
III.
CONCLUSION
For the reasons stated above, the Court hereby construes the claim terms as
follows:
the claim term “gastric fluid,” as used in the specified claims of the ‘475 and ‘280
Patents, means “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;”
the claim term “remains substantially intact,” as used in the specified claims of the
‘475 and ‘280 Patents, means “a polymeric matrix in which the polymer portion
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;”
the claim term “until all of said drug is released,” as used in the specified claims of
the ‘475 Patent, means “[until] 100% of the drug has been released;”
the claim term “said polymeric matrix being one the swells upon imbibition of
water thereby attaining a size large enough to promote retention in the stomach during
said fed mode,” as used in claim 1 of the ‘475 Patent, means “the dosage form, which
comprises a polymeric matrix, increases in size due to the ingress of water, such that
68
when the dosage form is introduced into the stomach in the fed mode, the dosage form
remains in the stomach for several hours;”
the claim term “said polymeric matrix being one that swells upon imbibition of
gastric fluid to a size large enough to promote retention in the stomach during said fed
mode,” as used in claim 43 of the ‘475 Patent, means “the dosage form, which comprises
a polymeric matrix, increases in size due to the ingress of gastric fluid, such that when the
dosage form is introduced into the stomach in the fed mode, the dosage form remains in
the stomach for several hours;”
the claim term “when swollen in a dimensionally unrestricted manner as a result of
imbibition of water,” as used in claim 1 of the ‘280 Patent, is construed to have its plain,
ordinary meaning;
the claim term “when swollen in a dimensionally unrestricted manner as a result of
imbibition of gastric fluid,” as used in claim 43 of the ‘280 Patent, is construed to have its
plain, ordinary meaning;
the claim term “is of a size exceeding the pyloric diameter in the fed mode to
promote retention in the stomach during said fed mode,” as used in the specified claims
of the ‘280 Patent, means “such that when the dosage form is introduced into the stomach
in the fed mode, the dosage form remains in the stomach for several hours;”
the claim term “releases substantially all of said drug within about eight hours
after such immersion,” as used in the specified claims of the ‘475 and ‘280 Patents,
means “at least 80% of the drug has been released after eight hours of immersion in
gastric fluid;”
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the claim term “releases substantially all of said drug after such immersion,” as
used in claim 1 of the ‘280 Patent, means “at least 80% of the drug has been released
after immersion in gastric fluid;”
the claim term “releases substantially all of said drug within about ten hours after
such immersion,” as used in the specified claims of the ‘475 and ‘280 Patents, means “at
least 80% of the drug has been released after ten hours of immersion in gastric fluid;”
the claim term “until substantially all of said drug is released,” as used in claim 1
of the ‘280 Patent, means “at least 80% of the drug has been released;”
the claim term “while releasing substantially all of said drug within said stomach
where said drug is maintained in an acidic environment,” as used in the specified claims
of the ‘475 and ‘280 Patents, means “at least 80% of the drug has been released after
immersion in gastric fluid;”
the claim term “about 4,500,000 to about 10,000,000,” as used in the specified
claims of the ‘475 and ‘280 Patents, means “3,600,000 to 12,000,000;” and
the claim term “about 5,000,000 to about 8,000,000,” as used in the specified claims
of the ‘475 and ‘280 Patents, means “4,000,000 to 9,600,000.”
The Court will issue an appropriate order.
s/ Mary L. Cooper
MARY L. COOPER
United States District Judge
Dated: April 6, 2017
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