Daravita Limited v. Actavis Laboratories FL Inc.
MEMORANDUM. Signed by Judge Gregory M. Sleet on 2/24/2017. (mdb)
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF DELAWARE
RECRO GAINESVILLE LLC,
ACTAVIS LABORATORIES FL, INC.,
Civil Action No. 14-1118-GMS
In this patent infringement action, Plaintiff Recro Gainesville LLC ("Recro") alleges
infringement byActavis Laboratories FL, Inc. of U.S. Patent No. 9,132,096 ("the '096 patent")
and U:S. Patent No. 6,902,742 ("the '742 patent"). 1 The court held a three-day bench trial in this
matter on October 3, 4 and 7 of2016. (D.I. 133-135). Presently before the court are the parties'
post-trial proposed findings of fact and conclusions oflaw concerning infringement of the patentsin-suit. (D.I. 125, 126).
Pursuant to Federal Rule of Civil Procedure 52(a), and after having considered the entire
record in this case and the applicable law, the court concludes that: (1) Actavis' proposed ANDA
products infringe all of the asserted claims of the '096 patent; and (2) Actavis' proposed ANDA
products infringe all of the asserted claims of the '742 patent.
These findings of fact and
conclusions oflaw .are set forth in further detail below.
Recro and Actavis submitted a Stipulated Dismissal of Claims and Counterclaims with Respect to U.S. Patent No.
6,228,398. (D.I. 117at1).
FINDINGS OF FACT2
Plaintiff Recro Gainesville LLC ("Recro") is a Massachusetts limited liability company
having its principal place of business at 1300 Gould Dr., Gainesville, GA 30504.
Defendant Actavis Laboratories FL, Inc. ("Actavis") is a Florida corporation having its
principal place of business at 2945 W. Corporate Lakes Blvd, Weston, FL.
The court has subject matter jurisdiction, as well as personal jurisdiction over all parties.
Recro has alleged infringement of U.S. Patent Nos. 6,902,742 (''the '742 patent") and
9,132,096 ("the '096 patent") against Actavis under 35 U.S.C. § 271(e)(2)(A).
Actavis asserted a defense of non-infringement of both the '096 and '742 patent.
The '742 patent, entitled "Multiparticulate Modified Release Composition," issued on
_June 7, 2005, to Dr. Devane, Dr. Stark, Mr. Fanning, and Dr. Rekhi as named inventors. The face
of the ·'742 patent claims priority to U.S. Patent Application No. 60/106,726, filed on November
2, 1998. According to the Orange Book, the expiration date of the '742 patent is November 1,
The '096 patent, entitled "Abuse Resistant Pharmaceutical Compositions," issued on
September15, 2015, naming Dr. Rekhi and Dr. Richard Sidwell as inventor~. The face of the
'096 patent claims priority to September 12, 2014. According to the Orange Book, the expiration
date of the '096 patent is September 12, 2034.
1. The Asserted Claims
a. '096Patent,:Claims1, 4, and 5
Claim 1, 4, and 5 of the '096 patent read:
1. An oral pharmaceutical composition comprising a first population of beads and a second
population of beads; said first bead population comprising a pharmaceutically active ingredient
Prior to trial, the parties submitted an exhibit of uncontested facts in conjunction with their Pretrial Order.
(D.I. 114, Ex. 1.) The court takes most of its findings of fact from the parties' uncontested facts. The court has also
reordered and renumbered some paragraphs, corrected some formatting errors, and made minor edits for the purpose
of concision and clarity that it does not believe alters the meaning of the paragraphs from the Pretrial Order. Otherwise,
any differences between this section and the parties' statement of uncontested facts are unintentional.
The court's findings of fact with respect to matters that were the subject of dispute between the parties are
included in Part III of this opinion ("Discussion and Conclusions of Law"), preceded by the phrase "the court finds"
or ''the court concludes."
selected from the grou consisting ofhydrocodone and pharmaceutically acceptable salts thereof,
wherein said first bead population is substantially free of polyethylene oxide; and said second
bead population comprising polyethylene oxide and a permeable or semi-permeable coating
selected from the group consisting of an ammonio methacrylate copolymer, a methacrylic acid
copolymer and a mixture thereof, wherein said second bead population is substantially free of
any pharmaceutically active ingredient.
4. The composition according claim 1, wherein the pharmaceutically active ingredient is
5. The composition according to claim 4, wherein the hydrocodone bitartrate is present in an
·amount of from 5 to 250 mg.
b. '742 Patent, Claims 1, 6, 13, 14, 16, and 19
Claims 1, 6, 13, 14, 16, and 19 of the '610 Patent read:
1. A multiparticulate modified release composition comprising a first population of active
ingredient-containing particles and at least one subsequent population of active ingredientcontaining particles, the active ingredient contained in the first population being an opiate and
the active ingredient in the subsequent populati9n being an opiate or non-opiate, wherein the
subsequent population of active ingredient-containing particles further comprise a modified
release coating or, alternatively or additionally, a modified release matrix material, such that the
composition following oral delivery to a subject delivers the active ingredients of the first and
subsequent populations in a pulsatile manner.
6. The composition according to claim 1, wherein the subsequent population comprises opiatecontaining particles.
13. The composition according to claim 6, wherein at least one of the active ingredients of the
first and subsequent populations comprises hydrocodone or a pharmaceutically acceptable salt
thereof, an enantiomer or mixtures thereof, or mixtures thereof.
14. The composition according to claim 1, wherein the first and subsequent populations have
different in vitro dissolution profiles.
16. The composition according to claim 15, which in operation releases substantially all of the
active ingredient from the first population prior to release of the active ingredient from the
19. The composition according to claim 16, wherein the mean in vitro dissolution profile in an
aqueous medium is such that substantially all of the active ingredient of the first population is
released within about two hours ..
Zohydro® ER extended-release capsules contain hydrocodone bitartrate and are
indicated "forthe management of pain severe enough to require daily, around-the-clock, longterm opioid treatment and for which alternative treatment options are inadequate." Recro licenses
the '742 and '096 patents to Pernix Therapeutics Holdings, Inc. ("Pernix") and Pernix markets
and sells Zohydro® ER capsules in the United States.
The '742 and '096 patents have been listed in the Orange Book in connection with
Zohydro® ER capsules.
Actavis submitted ANDA No. 206952 to the FDA seeking approval to market
hydrocodone bitartrate extended-release capsules in the 10, 15, 20, 30, 40, and 50 mg strengths.
By letter dated August 12, 2014, Actavis advised Recro's predecessor that it had
submitted ANDA No. 206952 to the FDA seeking approval to manufacture, use, or sell generic
hydrocodone bitartrate extended-release capsules in the 10, 15, 20, 30, 40, and 50 mg strengths
prior to the expiration of the '742 patent.
By letter dated April 6, 2015, Actavis advised Recro that it had submitted an amendment
to ANDA No. 206952 seeking approval to manufacture, use, or sell generic hydrocodone
bitartrate extended-release capsules in the 10, 15, 20, 30, 40, and 50 mg strengths prior to the
expiration of the'742 patent.
By letter dated November 10, 2015, Actavis advised Recro that it had submitted ANDA
No. 206952 to the FDA seeking approval to manufacture, use, or sell generic hydrocodone
bitartrate extended-release capsules in the 10, 15, 20, 30, 40, and 50 mg strengths prior to the
expiration of the '096 patent.
Recro asserts infringement of the following claims against Actavis: claims 1-4, 6, 9, 1314, 16 and 19 of the '742 patent; and claims 1-2 and 4-5 of the '096 patent.
C.A. No. 14-1118-GMS commenced on September 3, 2014, before the expiration of 45
days from receipt of Actavis's August 12, 2014 notice letter. C.A. No. 15-413-GMS commenced
on May 21, 2015, before the expiration of 45 days from receipt of Actavis's April 6, 2015 notice
letter. C.A. No. 15-1196-GMS commenced on December 23, 2015, before the expiration of 45
days from Recro's receipt of Actavis's November 10, 2015 notice letter. The 30-month stay
deadline against Actavis is February 12, 2017.
DISCUSSION AND CONCLUSIONS OF LAW
The court has jurisdiction over the subject matter of this action pursuant to 28 U.S.C. §§
1331and1338(a). Venue is proper under 28 U.S.C. §§ 1391(b), (c), and (d), and 1400 (b). After
having considered the entire record in this case, the substantial evidence in the record, the parties'
post-trial submissions, and the applicable law, the court concludes that Actavis' proposed products
infringe all of the asserted claims of the '096 and '742 patents. The court's reasoning follows.
1. The Legal Standard
The determination of whether an accused method infringes a claim in a patent has two
steps: (1) construction of the claim to determine its meaning and scope; and (2) comparison of
the properly construed claim to the method at issue. See Tanabe Seiyaku Co. v. United States
Int'ITrade Comm'n, 109 F.3d 726, 731 (Fed. Cir. 1997) (citing Markman v. Westview
Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en bane), aff'd 517 U.S. 370 (1996)). The
patent owner has the burden of proving by a preponderance of the evidence that "every limitation
of the patent claim asserted to be infringed is found in the accused [method], either literally or by
equivalent." SmithKline Diag., Inc. v. Helena Lab. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988).
Under this standard, a patent owner does not have to produce "definite" proof of infringement,
but must instead demonstrate that "infringement was more likely than not to have occurred." See
Warner-Lambert Co. v. TevaPharms., USA, Inc., 418F.3d1326, 1341 n.15 (Fed. Cir. 2005)
(citing Advanced Cardiovascular Sys., Inc. v. Scimed Life Sys., Inc., 261 F.3d 1329, 1336 (Fed.
Cir. 2001)). The application of a patent claim to an accused product is a fact-specific inquiry.
See Kustom Signals, Inc. v. Applied Concepts, Inc., 264 F.3d 1326, 1332 (Fed. Cir. 2001).
Even if an accused product differs enough from the claimed product to preclude literal
infringement, the patent owner can establish infringement under the doctrine of equivalents.
Zelinski v. Brunswick Corp., 185 F.3d 1311, 1316 (Fed. Cir. 1999). The doctrine of equivalents
analysis seeks to determine "ifthere is equivalence between those elements of the accused
product and the claimed limitations of the patented invention that are not literally infringed." Id.
Elements of the allegedly infringing device and the claimed device are considered equivalent if
the differences between the elements are insubstantial. Id. "One test used to determine
'insubstantiality' is whether the element performs substantially the same function in substantially
the same way to obtain substantially the same result as the claim limitation." Id. at 1316-17.
In the ANDA context, 35 U.S.C. § 271(e)(2)(A) provides that it shall be an "artificial" act
of infringement to submit an ANDA "if the purpose of such submission is to obtain approval ...
to engage in the commercial manufacture, use, or sale of a drug ... claimed in a patent or the use
of which is claimed ina patent before the expiration of such patent." 35 U.S.C. § 271(e)(2)(A).
The filing of an ANDA only constitutes a technical act of infringement for "purposes of creating
case or controversy jurisdiction." Perring B. V. v. Watson Labs., Inc.-Florida, 764 F.3d 1401,
1408 (Fed. Cir. 2014). Once jurisdiction is established, the ultimate infringement inquiry is
determined by traditional patent law principles, requiring "a comparison of the asserted patent
claims against the product that is likely to be sold following ANDA approval." Id.
2. The '096 Patent
Recro asserts that Actavis' ANDA products infringe claims 1, 4, and 5 of the '096 patent.
The focus of the dispute concerns one claim limitation: "a permeable or semi-permeable coating
selected from the group consisting of an ammonio methacrylate copolymer, a methacrylic acid
copolymer and a mixture thereof." JTX3, col 30 11. 8-12. Recro argues that Actavis'
ethylcellulose-based coating is equivalent to the claimed polyacrylic coatings-"ammonio
methacrylate copolymer, a methacrylic acid copolymer and mixtures thereof." Id.; D.I. 126 at
20. Actavis contends that not only does their ethylcellulose-based coating fail to satisfy the
function-way-result test, see Zelinski, 185 F .3d at 1316-17, it also includes a cellulosic polymer
that Recro dedicated to the public and other excipients not permitted by the claims. (D.I. 125 at
a. Dedication to the Public
Actavis maintains that Recro dedicated ethylcellulose to the public because cellulosic
polymers were disclosed in the specification, but not claimed. (D.I. 125 at 8). Disclosure
dedication occurs when the patentee "discloses but declines to claim subject matter." Johnson &
JohnstonAssocs. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1054 (Fed. Cir. 2002). Allowing the
patent holder to then recapture that subject matter under the doctrine of equivalents conflicts with
a patent claim's purpose to clearly define the scope of the patentee's right. Id. The Federal
Circuit has held, however, that the written description's disclosure of alternatives to the claimed
subject matter does not always dedicate those alternatives to the public. See id. ("Jhis
'disclosure-dedication' rule does not mean that any generic reference in a written specification
necessarily dedicates all members of that particular genus to the public."). The disclosure in the
specification must be specific enough that a skilled artisan "could identify the
has been disclosed and not claimed." Id. The court does not find that the disclosure of cellulosic
polymers dedicates ethylcellulose to the public.
The court heard testimony that ethylcellulose is one of many cellulosic polymers known
to those having ordinary skill in the art. Dr. Siepmann testified that there are many thousands of
cellulosic polymers in existence, and several dozen that are commonly used in pharmaceutical
formulations. Trial Tr. 113:19-114:2. After mentioning that suitable coating materials include
cellulosic polymers generally, the patent lists types of those polymers "such as cellulose acetates,
cellulose alkanylates and cellulose acrylates." JTX3, col. 5 11. 13-15. Dr. Felton, Actavis'
expert, stated that ethyl cellulose would not fall into any of the subcategories listed after the
disclosure of general cellulosic polymers." Trial Tr. 364:1-365:5. The court is therefore
persuaded by Recro's point that, though those having skill in the art might recognize
ethylcellulose as one choice of cellulosic polymer, the specification actually leads one away from
that choice. (D.I. 126 at 9).
The written description and the claims provide notice to the public "as to the subject
matter of the patent," and "the scope of the invention," respectively. PSC Computer Prod., Inc.
v. Foxconn Int'l, Inc., 355 F.3d 1353, 1358 (Fed. Cir. 2004). The quintessence of such public
notice is the ability to determine what has been taught by the specification and what has been
claimed. See id. at 1360. The court finds that a person skilled in the art would not have been
able to clearly identify that ethylcellulose was disclosed and not claimed, given the generality of
the phrase "cellulosic polymers." The court finds, the:refore, that ethylcellulose was not
dedicated to the public.
Doctrine of Equivalents
Recro concedes that the Actavis does not literally infringe the asserted claims of the '096
patent. (D.I. 126 at 5).
Instead, Recro contends that Actavis' ethylcellulose-based coating "is
equivalent to the claimed coatings 'consisting of an ammonio methacrylate copolymer, a
methacrylic acid copolymer and mixtures thereof."' (D.I. 126 at 4 (citing JTX3, col. 30 11. 812)). The court finds Recro's argument persuasive because the ethylcellulose-based coating
performs substantially the same function, in substantially the same way, to obtain the same
result. See Zelinski, 185 F .3d at 1316-17.
The specification of the '096 patent explicitly states that the functions of the placebo bead
coating are to "provide a physical barrier essentially separating or sequestering the gelling agent
from the other components of the composition" and to "control (i.e. delay or otherwise limit) the
ingress of water into the second bead population, thus restraining the gelling action of the gelling
agent." JTX3, col. 4, I. 66-col. 5, I. 6. Defendants' expert, Dr. Felton, testified that
ethylcellulose "is the semipermeable membrane that controls the water ingress into the bead."
Trial Tr. 296:20-22. Defendants ANDA also characterizes ethylcellulose as a polymer "widely
used in oral pharmaceutical formulations as a binder, extended release polymer and hydrophobic
coating agent for tablets and granules." JTX35 at 31. Additionally, in discussing the_effect of
the pH of the dissolution medium on drug release, Actavis explained to the FDA that
ethylcellulose was selected as the "release controlling polymer" because, in the presence of
liquid, it exhibits "pH independent swelling and permeating of drug molecules across the ·
membrane." JTX35 at 21. The court finds that Defendants statements in the ANDA and Dr.
Felton's testimony support Plaintiffs' assertion that the ethylcellulose-based coating performs the
same function as the claimed polyacrylic coatings. See Bayer AG v. Elan Pharm. Research
Corp., 212 F.3d 1241, 1248 (Fed. Cir. 2000) (holding that courts can consider statements made
in the ANDA to instruct their infringement analysis).
The claimed polyacrylic coating behaves differently depending on how it is used. When
the claimed composition is administered orally and intact the "[w]ater from the surrounding
environment is absorbed·through the coating of the gelling agent-containing beads which, upon
contact with the gelling agent, causes the beads to swell." JTX3, col. 9 11. 33-36. Eventually,
the swelling of the beads causes the coating to rupture. Id. 11. 36-38. Though rupture of the
gelling-agent containing beads causes the gelling agent to form a viscous mass, the gel does not
interfere with the release of the drug from the active ingredient-containing beads when taken as
directed. Id. 11. 45-49. This is due to how the bead population disperses along the
gastrointestinal tract. Id. 11. 31-33. When the claimed composition is crushed or dissolved in a
small amount of water, however, the gelling agent creates a viscous mass, trapping the active
ingredient, and assuring that it cannot be drawn up into a syringe. Id. 11. 50-55.
Defendant's expert, Dr. Felton, testified that ethylcellulose in Actavis' placebo beads
functions to restrict the ingress of fluid into the bead and is often used in the preparation of
pharmaceutical coatings capable of rupture. Trial Tr. 355:17-25. Therupturablenature of the
ethylcellulose-based coating is clear from the examples adduced at trial demonstrating the
"rupture sequence" of both an ethylcellulose based coating and the methacrylate coating. PTX
56 (methacrylate coating); PTX 68 (ethylcellulose coating). The sequences appear substantially
similar, if not identical. ·
Dr. Felton explained that the way Actavis' product works is that if it is ingested as a
capsule, "the capsule [will] dissolve, and the individual beads, both drug containing bead and
placebo, a gelling bead, will separate, and as long as they separate sufficiently far away from
each other, then they won't interfere with the release of the active ingredient." Trial Tr. 354:1925. Dr. Felton agreed with Plaintiffs counsel that Actavis' product has abuse deterrent
properties without changing the in vitro release ofhydrocodone when the product is used as
intended. Trial Tr. 355:1-5. The Addendum to Product Development Report for Actavis'
generic product supports Dr. Felton's testimony, attesting to the fact that "[t]he presence of
placebo beads is not intended to alter the drug sequence." JTX35 at 20. The court finds that the
combination of the statements in the ANDA along with Dr. Felton's testimony is enough to
conclude that Actavis' ethylcellulose-based coating functions in substantially the same way as
the claimed coating.
Lastly, the result of the polyacrylic coating in the placebo bead is that it deters abuse
when the product is crushed or dissolved in a small amount of water. See Trial Tr. 111: 11-13.
When taken as directed, however, it allows the patient to receive the same in vivo activeingredient exposure as they would without the coating. Id. Dr. Felton testified that Actavis'
placebo beads achieve the same result. See Trial Tr. 355:1-5.
Defendants argue Plaintiffs failed to prove infringement under the doctrine of equivalents
because Plaintiff's expert, Dr. Siepmann, did not properly account for the excipients in Actavis'
coating. (D.I. 125 at 11). Defendants contend that because the claim language requires the
coating be "selected from the group consisting of an ammonio methacrylate copolymer, a
methacrylic acid copolymer and a mixture thereof," the presence of any other excipients is
explicitly excluded. Id. The court is not persuaded.
The court finds that excipients are not excluded by the language of claim 1 of the '096
patent. In Warner Chilcott Co., LLC v. Zydus Pharmaceuticals (USA) Inc., No. CA 11-1105RGA, 2013 WL 1729383 (D. Del. Apr. 22, 2013), Judge Andrews confronted a very similar
issue to the one the court faces here---does a Markush group limit "the entirety of the 'inner
coating layer' to the specifically listed polymers?" Id. at *5. Judge Andrews concluded that a
person having ordinary skill in the art would not find excipients excluded from the Markush
claim because excipients, solvents, and carriers are "naturally associated with pharmaceutical
Excipients, therefore, could be understood to be unrelated to the actual
invention because they were not used in a novel fashion. Id. The court finds that identical
reasoning can be applied here.
Although the claim phrase "consisting of' is ordinarily found to signify exclusion, in the
'096 patent, "consisting of' only serves to iimit the universe of polymers that can be present in
the coating. The phrase does not limit the presence of excipients, solvents or carriers ubiquitous
to pharmaceutical preparations. Dr. Felton testified that triethyl citrate was a common excipient
in drug coatings. Trial Tr. 360:7-8. The '096 patent itself also states that "[t]he coating may
further comprise plasticizers, pore forming agents, anti-adherents or other excipients." JTX3,
col. 5 11. 24--26. The court thus finds that excipients like talc and triethyl citrate are not excluded
by Markush claim style.
Defendants maintain that because triethyl citrate is a pore former, its presence in Actavis'
placebo bead coating could impact its function, undermining the doctrine of equivalents analysis.
(D.I. 125 at 11-12). The court finds Defendant's argument unconvincing given its statements in
the ANDA. Defendants acknowledged that triethyl citrate could alter the permeability
characteristics of the coating. JTX030 at 51. They represented to the FDA, however, that "the
risk of [t]riethyl [c]itrate affecting dissolution is low because it's [sic] level of use in the current
formulation is fixed at 10 weight percent of the ER." Id. In fact, Defendants explicitly stated
that both triethyl citrate and talc have a "negligible effect on drng dissolution." Id. at 56. As a
result, the court finds that the presence of excipients in Actavis' coating does nothing to
undermine the doctrine of equivalents analysis.
Dependent Claims 4 and 5
There is really no dispute that Actavis' ANDA product meets the limitations of
dependent claims 4 and 5. Claim 4 discloses "[t]he composition according to claim 1, wherein
the pharmaceutically active ingredient is hydrocodone bitartrate." JTX3, col. 3011. 19-20.
Claim 5 requires a "composition according to claim 4, wherein the hydrocodone bitartrate is
present in an amount of from [sic] 5 to 250 mg." JTX3, col. 30 11. 21-23.
Actavis' ANDA document discloses a "[q]uality [t]arget [p]roduct [p]rofile (QTPP) for
[h]ydrocodone [b]itartrate ER [c]apsules" where the dosage strength is 10, 15, 20, 30, 40, and 50
milligrams. JTX30 at 4, 16-17. The court thus finds that Actavis' ANDA product infringes
dependent claims 4 and 5 in addition to independent claim 1.
3. The '742 Patent
Recro asserts that Actavis' product infringes claims 1, 6, 13, 14, 16, and 19 of the '742
patent. The dispute centers around two claim limitations: (1) "comprising a first population of
active ingredient-containing particles and at least one subsequent population of active ingredientcontaining particles," JTX2 col. 15 11. 61-64; and (2) "delivers the active ingredients of the first
and subsequent populations in a pulsatile manner." Id. col. 1611. 4-5. Recro argues that
Actavis' products literally infringe both claim limitations, and alternatively that Actavis' product
infringes the first claim limitation under the doctrine of equivalents. (D.I.126 at 12-15).
a. A first and subsequent population of active ingredientcontaining particles
The '742 patent specification lists a multitude of multiparticulate modified release
compositions. The patent states that typically, "the dosage form may be a blend of different
populations of active ingredient containing particles which make up the immediate release and
the modified release components, the blend being filled into suitable capsules." JTX2, col. 10 11.
38-42. The patent also explains that the different populations of active ingredient-containing
particles can be compressed into "mini-tablets," or further, formed into a multilayer tablet. Id. 11.
The evidence presented at trial demonstrated that Actavis' active ingredient-containing
beads do not comprise a first and subsequent population of active ingredient containing particles.
Instead, Actavis' product can be described as a multilayer tablet. Dr. Felton described a tablet
where a drug layer, containing hydrocodone, polyethylene glycol, and water, is layered on top of
a sugar sphere. Trial Tr. 309:21-312:25. A release controlling barrier is subsequently layered
on top of the drug layer, and on top of the barrier layer, there is another drug layer, again with
hydrocodone bitartrate, polyethylene glycol, and water. Id. Recro argues that Actavis' product
still falls within the scope of the claim because the specification explicitly allows for a multilayer
tablet. The patent makes clear, however, that the first and second population of-particles are
different from each other-"the subsequent population of active ingredient-containing particles
further comprises a modified release coating or, alternatively or additionally, a modified release
matrix material." JTX2, col. 15 11. 67-col. 1611. 3. As Dr. Felton stated, both active ingredient
layers are the same. The subsequent drug layer, as Dr. Felton called it, does not comprise a
modified release coating or a modified release material. The release-controlling barrier layer is
on top of the layer containing the active-ingredient.
Recro argues that Actavi.s' product does, in fact, have two populations of active
ingredient-containing particles-one with a sugar sphere, a drug layer, and an extended release
coat and another with just a sugar sphere and a drug layer. (D.I. 126 at 13-14). Dr. Siepmann,
Recro's expert, testified that what Actavis' essentially did was take the "particle" without the
extended release coat and put it on to the "particle" with the extended release coat. Trial Tr.
85:12-20. The court finds Recro's argument unpersuasive. The claim requires that the particles,
plural, comprise a modified release coating. JTX2, col. 15 ll. 67-col. 16 11. 3. According to Dr.
Siepmann's testimony, there would only be one active ingredient-containing particle with an
extended release coating in each of Actavis' pellets. Thus, from a semantic perspective, a sugar
sphere with a drug layer and an extended release layer cannot be considered a subsequent
population of active ingredient-containing particles.
In the alternative, Recro tries to argue that the active-ingredient-containing particles are
the individual particles of hydrocodone contained in Actavis' pellets. Again, the court is not
persuaded. Hydrocodone bitartrate is present in the pellets as a crystal. Even Dr .. Siepmann,
refers to the active ingredient as a drug crystal. Trial Tr. 91 :5-6. It is unclear to the court what
could be considered an active-ingredient containing particle in a layer that could more aptly be
described as a population of polyethylene glycol, water, and drug crystals. Moreover, claim 1 of
the '742 patent requires that the active ingredient-containing particles themselves comprise the
modified release coating or the modified release matrix material. JTX3, col. 1611. 1-3. · Recro
offers no arguments for how that is possible given their alternate construction for active
Because the court concludes that Actavis does not literally infringe the first and
subsequent population of active ingredient-containing particles limitation, it must determine
Actavis infringes under the doctrine of equivalents. Recro maintains that, even
assuming Actavis' product does not contain a first and subsequent population of active
ingredient-containing particles, there is no substantial difference between Actavis' approach and
the claimed approach. (D.I. 126 at 14). Dr. Siepmann testified that the function and result of
both.the one- and two-pellet approach are to "deliver the drug in a specific manner," i.e. a
pulsatile manner. Trial Tr. 87:8-10, 25-88:1. The court finds that the active ingredient in
Actavis' product, with first and subsequent active ingredient-containing layers separated by a
release-controlling barrier, is delivered in a pulsatile manner, see infra § III.A.3.b-c.
Accordingly, the court moves on to analyzing whether pulsatile delivery is achieved in the same
way by the claimed product and Actavis' product.
The specification of the '742 patent makes clear that active ingredient is released from
the first population of active ingredient-containing particles, followed by ~ subsequent release of
active ingredient-containing from the second population of particles. JTX2, col. 411. 37--48. The
patent also allows for situations where the first population releases the active ingredient rapidly
and the second population releases the active ingredient over an extended period of time. JTX2,
col.8 11. 35--44. The ANDA reveals a very similar mode of action. In Actavis' product, the
"two-stage coating" works by releasing twenty percent of the total dose immediately, followed
by the extended release of eighty percent of the dose. JTX20 at 20. So regardless of whether the
first and subsequent releases of active ingredient come from different layers of one multilayer
tablet or different particles all together, the releases are achieved in the same way; the first
release occurs from the first population ofparticles or a first layer, and a subsequent release
occurs from a second population of particles or a second layer. Because the court finds that
Actavis' multilayer tablet differs insubstantially from Recro's claimed first and subsequent
population of active ingredient-containing particles, Actavis' product meets the first limitation of
The court wishes to note that the La Manna reference played no role in its analysis. It is
not clear to the court whether Actavis is trying to use the reference to assert a theory of
prosecution history estoppel or whether Actavis is simply trying to underscore its point that its
multilayer tablet with a discrete barrier layer would not be equivalent to claimed dosage form.
(D.I. 125 at 14). Either way, the statements made to the Patent Office during the prosecution of
the La Manna application have no effect on Recro' s ability to assert infringement under the
doctrine of equivalents. See Festa Corp. v. Shoketsu Kinzoku Kogyo Kabushild Co., 535 U.S.
722, 734 (2002) (explaining that ifthe original patent application once claimed the purported
equivalent, but during patent prosecution the patentee narrowed the claim to obtain the patent,
the patentee cannot later recapture that subject matter through the doctrine of equivalents).
The statements made with regard to the La Manna reference were made on January 11,
2007, long after the '742 patent issued on June 7, 2005. See id. at 724 ("Estoppel arises when an
amendment is made to secure the patent and the amendment narrows the patent's scope.").
Though prosecution history of a related application may limit application of the doctrine of
equivalents in a later filed patent, Al-Site Corp. v. VSI Int'!, Inc., 174 F.3d 1308, 1322 (Fed. Cir.
1999) (emphasis .added), it can by no means affect the application of the doctrine of equivalents
in an earlier filed patent without vitiating the very purpose of the doctrine. Here, the statements
clearly were not made to secure the patent considering they. were made after the '742 patent
issued. For that reason, the court declines to consider the statements made to the Patent Office
during prosecution of the La Manna patent.
b. Delivers the active ingredients of the first and
subsequent populations in a pulsatile manner
Claim 1 of the '742 patent requires that following oral delivery, the composition "delivers
the active ingredients of the first and subsequent populations in a pulsatile manner." JTX2, col.
1611. 4-5. The court's December 29, 2015, claim construction order construed the phrase to
mean "following oral delivery to a subject provides a first pulse of an active ingredient release,
followed by at least one subsequent pulse of active ingredient release, producing a plasma
concentration profile characterized by two or more peaks interspersed with low concentration
troughs." (D.I. 69 at 1-2).
Recro argues that Actavis' dissolution data disclosed in the ANDA demonstrated that the
· release from its products involves two pulses of active ingredient. (D.I. 126 at 16). Actavis
counters that the term "pulse" would be synonymous with "burst" to a person of skill in the art.
Trial Tr. 329:23-24. The court finds that regardless of what a person having ordinary skill in the
art would interpret the term "pulse" to mean, a "burst" of active ingredient is not required by the
patent or the court's claim construction. See Phillips v. A WH Corp., 415 F.3d 1303, 1313 (Fed.
Cir. 2005) ("[T]he person of ordinary skill in the art is deemed to read the claim term not only in
the context of the particular claim in which the disputed term appears, but in the context of the
entire patent, including the specification."). Accordingly, the court finds Actavis' argument
unpersuasive on this point.
The '742 patent explains that "[t]he number of pulses in the profile ... in operation will
depend on the number of active ingredient containing components in the composition." JTX2,
col. 6 11. 16-19. Embodiments listed in the patent specification also allow for a number of
combinations of active ingredient-containing components. The first component can be an
immediate release or a time-delayed immediate release component. JTX2, col. 8 11. 5-10. The
second component can be a time-delayed immediate release, a timf'.-delayed sustained release or
an extended release component. JTX2, col. 8 11. 11-16. Because the patent states that the
number of pulses will depend on the number of active ingredient-containing components, and
such an interpretation does not interfere with the court's claim construction ruling, the court
finds that Actavis' product meets that limitation.
Actavis' ANDA states that the goal of the company's research and development efforts
was to create a dosage form that provided an initial rapid release followed by a sustained release.
JTX30 at 46. They achieved that goal by "loading 80% of the dose onto active pellets that were
coated with an ER coat" and then, on top of the ER coat, applying "an over-coat of
[h]ydrocodone [b]itartrate equivalent to 20% of the dose." Id. The type of active ingredientcontaining comp-onents used in Actavis' product-immediate and extended release
components-fall within the scope of claim 1 of the '742 patent. Interpreting the claim term
"pulse" in accordance with Dr. Felton's proposed construction-essentially requiring two
immediate-release components-would cause a preferred embodiment to fall outside of the
claim scope. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed. Cir. 1996)
(explaining that an interpretation that reads a preferred embodiment out of the claim scope is
rarely, if ever, correct). Because Actavis' product contains two active ingredient-containing
components falling within the scope of claim 1, as evidenced by its statements in the ANDA, the
court finds that Actavis product meets the first and subsequent pulse claim limitation in claim 1
of the '742 patent.
The applicant's discussion of the Paradissis reference during prosecution of the parent of
the '742 patent, U.S. Patent No. 6,228,398, does nothing to undermine the court's findings. The
Paradissis reference taught a pharmaceutical composition "comprising 0-50% of an immediate
release particle and up to 100% of an extended release particle capable of approaching a zero
order release rate of a drug during a 12 to at least 24 hour period." DTX512 at 5. The applicants ·
explained that a zero order release rate meant that the drug was released at a constant rate over
time. Id. The Applicants contrasted that release rate with the pulsatile release of their own drug,
which, they stated, "means a first pulse ·of active ingredient release is followed by a period of
negligible active ingredient release, the period of negligible active ingredient rel~ase is followed
by at least one second pulse of active ingredient release." DTX512 at 5-6.
Actavis tries to argue that the period of negligible release is somehow required by the
claims because of the applicant's statements with regard to this parent application. (D.I. 125 at
· 17). Actavis also interprets the term "zero-order release rate" to mean a "sustained release
system designed to release the drug over an extended time frame." Id. First, the court's claim
construction does not require a negligible release of active-ingredient. (D.I. 69 at 1-2). Further,
the prosecution history establishes that Paradissis could be a one hundred percent extended
release particle with a constant release rate. Actavis' product is certainly not analogous to the
product disclosed in the Paradissis reference. Actavis' own ANDA states that the goal of their
research and development work was to "formulate a dosage form that provides an initial rapid
release followed by a sustained release," not a one hundred percent extended release particle.
JTX30 at 46. The Paradissis reference, therefore, has no effect on the court's infringement
analysis of the pulsatile release claim limitation.
c. Plasma concentration characterized by two or more
peaks interspersed with low concentration troughs
As previously mentioned, the court construed claim 1 to require not just a first and
subsequent pulse of active ingredient, but also "a plasma concentration profile characterized by
two or more peaks interspersed with low concentration troughs." (D.I. 69 at 2). Actavis
contends that its three bioequivalence studies show no evidence that administering its product to
patients causes plasma concentration profiles that meet the court's construction. (D.I. 125 at 1819). Recro argues, however, that because some patients experienced plasma concentration
profiles characterized by two or more peaks interspersed with low concentration troughs,
Actavis' product meets the claim limitation. (D.I. 126 at 18). The court finds Recro's argument
It is well established that a finding of direct infringement can be predicated on
circumstantial evidence demonstrating that at least one person directly infringed an asserted
claim. See Toshiba C01p. v. Imation Corp., 681F.3d1358, 1364 (Fed. Cir. 2012); Lucent
Techs., Inc. v. Gateway, Inc., 580 F.3d 1301, 1317 (Fed. Cir. 2009); i4i Ltd. P'ship v. Microsoft
Corp., 598 F.3d 831, 850 (Fed. Cir. 2010). Further, claim 1 of the '742 patent references "oral
delivery to a subject." The court construed "a subject" in accordance with its plain and ordinary
meaning. (D.I. 69 at n.1 ). The facts at issue here bear a striking resemblance to those analyzed
by Chief Judge Stark in Research Found. ofState Univ. ofNY. v. Mylan Pharm. Inc., 809 F.
Supp. 2d 296 (D. Del. 2011), vacated-in-part on other grounds, 531 F. App'x 1008 (Fed. Cir.
In Research Found., Mylan maintained that their generic drug did not infringe the
claimed drug because it did not meet the claim limitation requiring a "steady state blood
concentration of doxycycline of between 0.3 µg/ml to 0.8 µg/ml." Id. at 330. Mylan presented
evidence at trial that the mean minimum blood concentration value of 31 subjects was 0.164
µg/ml. Id. Chief Judge Stark found that the claims-at-issue were not directed to mean values,
however. The claims instead were directed to administering a single pill and treating a single
patient. Id. Accordingly, the court held that "even if only 1 of 31 subjects in the pivotal pK
study had a Cmin of 0.3 to 0.6 µg/ml, [that was] a sufficient basis from which to find
infringement." Id. at 330-31. The court finds Recro's analysis of individual subject's plasma
concentration profiles proper given Research Found. and the claim limitation's focus on
administering the composition to a subject.
Here, Recro presented evidence that at least seven individuals in the ACT-15030
bioequivalence study had plasma profiles exhibiting two or more high concentration peaks
interspersed with low concentration troughs. JTX41 at 2-7. The 15030 study reported subject's
plasma concentration levels between zero and thirty hours after they were given ~en milligrams
ofhydrocodone bitartrate extended release capsules. Id. Recro's expert, Dr. Fleckenstein,
showed that subject 1028 in the ACT-15030 study exhibited the claimed plasma concentration
profile. Trial Tr. 205:17-206:1.
Dr. Fleckenstein presented both the data from Actavis' 15030
clinical study report, JTX41at2, and his own graph of that data. PDX236. Dr. Fleckenstein
explained that subject 1028 exhibited a rapid absorption of the drug indicated by a sharp rise in
·hydrocodone concentration in the subject's blood-from zero concentration upon administration
to 7.613 hydrocodone concentration after two hours. JTX41 at 2; Trial Tr. 205:17-22. At three
hours, subject 1028 had a hydrocodone plasma concentration level of 6.927, a drop from the
peak experienced at two hours. Dr. Fleckenstein explained that this was the low concentration
trough required by claim 1 because it was consistent with the dissolution data reported in
Actavis' ANDA. Trial Tr. 229:5-14. 3
Dr. Fleckenstein summarized all of Actavis' in vitro dissolution tests found in Actavis'
ANDA. JTX45 at 51, 54, 57, 60, 63, 66, 117, 129, 141, 153, 165, 177; PDX223. The
dissolution data from the Clinical Summary section of the ANDA, for the six different dosage
forms (10mg-50mg), had sampling times at 0, 1, 2, 4, 6, 8, 10, 12, 14, and 16 hours. JTX45 at
51, 54, 57, 60, 63, 66. Dr.
testified that hydrocodone, being a highly soluble
compound, dissolves very rapidly. Trial Tr. 192:6-10. It was, therefore, important to have more
frequent sampling times than each hour. More frequent sampling was specifically needed for at
least the first four hours because that is when the dissolution rates are rapidly changing due to the
combination of and extended release layer and immediate release layer in Actavis' product.
Dr. Fleckenstein also pointed to data in the Zohydro® New Drug Application ("NDA"), JTXlO at 93, to support
his testimony that Actavis' ANDA product likely had a "two to two and a half hour lag time built in before release
of the second component." Trial Tr. 206:2-6. The court could not consider that data, however. "It is error for the
court to compare in its infringement analysis the accused product or process with the patentee's commercial
embodiment or other version of the product or process; the orily proper comparison is with the claims of the patent."
Zenith Labs v. Bristol-Myers Squibb Co., 19 F.3d 1418, 1423 (Fed. Cir. 1994). There is an exception to that maxim
where the commercial embodiment meets all of the claim limitations. See Adams Respiratory Therapeutics, Inc. v.
Perrigo Co., 616 F.3d 1283, 1288 (Fed. Cir. 2010). Upon analysis of the Zohydro® NDA, the court realized that it
likely made an error in its Markman Opinion. See (D.I. 69 at 1-2). As previously mentioned, the court construed
''pulsatile manner" in claim 1 of the '742 patent to mean "producing a plasma concentration profile characterized by
two or more peaks interspersed with low concentration troughs." Id. After analyzing the NDA, it appears that
Zohydo®, for which the '742 patent is listed in the Orange Book, does not even meet the pulsatile release claim
limitation as construed by the court. Figure 45 in the NDA-a graphical representation of the in vitro mean plasma
concentration levels ofhydrocodone over time-shows no sign of the "low concentration trough" required by the
court's construction. JTXlO at 81. During claim construction, the court did not have the benefit of the data
disclosed in the NDA, however. To be clear, Actavis' product infringes the "pulsatile" limitation of claim 1 as the
court construed it. The court simply wishes to note that: (1) it is possible that the court's construction of"pulsatile
manner'' would have been different ifthe NDA had been before it during claim construction; and (2) it would
constitute clear error for the court to credit Dr. Fleckenstein's testimony comparing Actavis' product to Zohydro®.
Trial Tr. 249:5-9. Dr. Fleckenstein used the control group data from Actavis' alcohol dose
dumping study to get more frequently sampled data for his analysis of the dissolution rate of
Actavis' product. Id. at 192:13-16.
The table that Dr. Fleckenstein created, using both the alcohol dose dumping control
group data and the general dissolution studies' mean data, demonstrates that in the first fifteen
minutes after administration of the ANDA product, nineteen percent of the hydrocodone
dissolved. PDX224; Trial Tr. 193:16-21. Over the next fort-five minutes, another nineteen
percent slowly dissolved. Trial Tr. 193 :22-25 ..Between one and four percent dissolved every
fifteen minutes until the two-hour time-point. PDX224. Between two and four hours, and
additional twenty-five percent of the total hydrocodone dissolved. Id. Between the four- and
six-hour time-points, only another thirteen percent of the total hydrocodo:µe dissolved. Id. The
court finds that Dr. Fleckenstein's analysis of the dissolution data shows an immediate release
between zero and fifteen minutes. Id. There is then a slower rate of release over the next hour
and forty-five minutes, where only another nineteen percent in total is released. Id. There is
then another release somewhere between the two- and four-hour time-points because the percent
dissolved increased during that two-hour window. Id. After the four-hour time-point, the
amount ofhydrocodone dissolved between each time-point slowly declined. Id. The court finds
that Dr. Fleckenstein's testimony, along with the dissolution data, support the assumption that
the dip in subject 1028's plasma profile actually reflects the low-concentration trough required
by the claims. If there is another release ofhydrocodone from the subsequent layer between two
and four hours after administration, it follows that there would be a dip in the amount of
hydrocodone present in the subject's blood prior to that release because the body has
metabolized most of the initial release. See Trial Tr. 217:22-218:24.
Some subjects, like subject 1018, exhibited low concentration dips in their blood plasma
profiles after 4 hours. JTX41 at 2, 5. Dr. Fleckenstein distinguishes those dips from the actual
low concentration trough associated with Actavis' drug delivery system by explaining that,
according to the clinical protocol, the subjects were fed after four hours. Trial Tr. 208:13-20.
Dr. Fleckenstein explained that food will "stimulate flow to the liver" and cause "variability in
the clearance of the drug." Id. The court finds Dr. Fleckenstein's testimony credible. It is also
buttressed by Actavis' own data stating that "[i]nter-assay precision of the assay was determined
by the % [coefficient of variation] ofthe [quality control] samples for Hydrocodone from all
acceptable batches and it ranged from 2.7 to 3.3%." JTX33 at 22. The high accuracy of the
assay employed directly contradicts Actavis' explanation for why the court must consider mean
subject plasma concentration data-"the assay that is.used could contribute to variability."
(D.I. 125 at 21). The court thus finds that Actavis' product meets the plasma profile limitation of
claim 1 of the '742 patent because at least some patients exhibited the claimed profile.
Actavis instructs the court to consider the mean values for the group of subjects because
of the variability in an individual's blood concentration over time. (D.I. 125 at 21); Trial Tr.
442:1-8. Again, the court finds that argument unavailing. Dr. Fleckenstein testified that because
of the complicated absorption characteristics for hydrocodone, there will be a lot of intra-subject
variability-each subject will absorb and metabolize the drug slightly differently. Trial Tr.
217:22-218 :24. If anything, the-intra-subject variability underscores the importance of
analyzing individual data because, as Plaintiff's Expert, Dr. Fleckenstein, testified, "the use of
mean values would 'average out' the variability and smooth out the profiles." (D.I. 126 at 18
(citing Trial Tr. 204:14-205:2)).
Actavis also takes issue with the fact that "Dr. Fleckenstein's conclusions rely on singlepoint dips in blood plasma concentration levels in 16 out of the 112 subjects in the three studies
conducted." (D.I. 125 at 21 ). Recro persuasively points out, however, that the patent does not
require a particular patent curve shape with specific peak height and trough depths. (D.I. 126 at
19). The patent explains that those in the art are aware that the plasma concentration curve will
be influenced by the active ingredient used, the delay in release of the active ingredient from
each component, the coatings used in or on the components, and the nature of release from the
components. JTX2, col. 8 IL 1-27. "Depending on the duration of the lag time between the
release of active ingredient from each component and the nature of the release ... the pulses in
the plasma profile may be well separated and clearly defined peaks ... or the pulses may be
superimposed to .a degree .... " JTX2, col. 8 IL 27-34. Neither the patent nor the court's claim
construction require a specific amount of time for which a peak or a trough must persist.
Actavis' arguments on this point do nothing to undermine the court's finding that Actavis'
product meets the claimed plasma profile limitation.
Dependent claims 6, 13, 14, 16, and 19
Dependent claim 6 of the '742 patent discloses the "composition according to claim 1,
wherein the subsequent population comprises opiate-containing particles." JTX2, col. 1611. 1517. Actavis' ANDA clearly states that the extended release layer comprises hydrocodone.
JTX35 at 28. Trial testimony established that hydrocodone bitartrate is an opioid. Trial Tr.
178:11-12. Actavis, therefore infringes claim 6 of the '742 patent.
Claim 13 of the '742 patent requires "[t]he composition according to claim 6, wherein
at least one of the active ingredients of the first and subsequent populations comprises
hydrocodone or a pharmaceutically acceptable salt thereof." JTX2, col. 1611. 36-40. The
ANDA establishes that both layers-the immediate release and extended release layers-of
Actavis' product comprise hydrocodone. JTX35 at 28.
Claim 14 requires "[t]he composition according to claim 1, wherein the first and
subsequent populations have different in vitro dissolution profiles." JTX2, col. 1611. 41--43.
The combination of the average dissolution data from Actavis' in vitro dissolution studies and
the more frequently sampled data from the alcohol dose dumping studies clearly indicate
different in vitro dissolution profiles for the immediate release and extended release components
of Actavis' product.
Actavis disclosed in its ANDA that the initial rapid release followed by a sustained
release was achieved "by loading 80% of the dose onto active pellets that were coated with an
ER coat," and then loading "[ o]n top of the ER coat, an over-coat of [h]ydrocodone [b ]itartrate
equivalent to 20% of the dose." JTX30 at 46. The average dissolution data that Dr. Fleckenstein
collated into a chart, PDX224, and a graph, PDX225, demonstrated that nineteen percent of the
hydrocodone in the product dissolved within the first 15 minutes of administration. JTX45 at
117, 129, 141, 153, 165, 177. Another nineteen percent dissolved over the next hour and fortyfive minutes. Id. At two hours, thirty-eight percent of hydro co done had dissolved, and at four
hours sixty-three percent had dissolved. JTX45 at 51, 54, 57, 60, 63, 66. The amount dissolved
slowly decreased for the remaining time points-6, 8, 10, 12, 14, and 16. Id. The rate of
dissolution was never as high as it was in the first fifteen minutes. Trial Tr. 193:16-21. The
dissolution data that Dr. Fleckenstein presented at trial clearly matched the goals of Actavis'
formulation as outlined in their ANDA. See JTX30 at 46. About twenty-percent of the drug
dissolved immediately, and the remaining eighty-percent of hydrocodone that came from the
layer behind the extended-release coating, dissolved slowly over the remaining fifteen hours and
forty-five minutes. JTX45 at 51, 54, 57, 60, 63, 66, 117, 129, 141, 153, 165, 177.
Dr. Fleckenstein also presented evidence allowing the court to conclude that the
immediate release of twenty-percent ofhydrocodone does, in fact, come from the first active
ingredient layer of Actavis' product, whereas the extended dissolution of eighty-percent of
Actavis' product comes from the subsequent active ingredient containing layer of Actavis'
product. PDX227. Dr. Fleckenstein analyzed the ANDA dissolution data for just the extended
release component of Actavis' drug. JTX43 at 2; JTX42 at 1. Dr. Fleckenstein testified that he
subtracted the dissolution percentage for the extended release form of the drug from the total
percentage dissolved at those time points disclosed in the in vitro dissolution studies. Trial Tr.
194:22-195:5. This analysis demonstrated that, in the first hour, most of the dissolution of the
drug comes from the first active-ingredient containing layer, with only an average ofninepercent of the extended release component contributing to the total amount dissolved. PDX227;
JTX43 at 1,2. Recro persuaded the court that it is more likely than not that Actavis' product
infringes claim 14 of the '742 patent.
Claim 16 discloses a form of the composition of claim 1 where "substantially all of the
active ingredient from the first population" is released "prior to release of the active ingredient
from the subsequent population." JTX2, col. 1611. 48-51. As previously mentioned, Actavis
loaded twenty-percent of the hydrocodone dose in a layer on top of the extended release layer.
Actavis intended for the top active ingredient-containing layer to release immediately upon
administration to the subject. JTX30 at 46. Dr. Fleckenstein's chart, PDX229, summarizing the
data disclosed in Actavis' ANDA, demonstrates that within the first fifteen minutes after
administration of the drug, nineteen-percent ofhydrocodone is dissolved. JTX45 at 117, 129,
141, 153,.165, and 177. The first active-ingredient containing layer in Actavis' product contains
twenty-percent of the total amount ofhydrocodone. The data also demonstrates that only an
average of nine-percent of the extended release component is released within the entire first
·hour. JTX35 at 42; PDX227. Accordingly, the court finds that the first active ingredient layer
released substantially all of the active-ingredient prior to the release of active ingredient from the
subsequent layer found under the extended release coating.
Claim 19 requires that mean, in vitro dissolution profiles demonstrate that "substantially
all of the active ingredient of the first population is released within about two hours." JTX2, col.
1611. 64-67. For the reasons previously stated, this claim is clearly infringed by Actavis'
product. In fact, substantially all of the active ingredient is released from the first active
ingredient-containing layer within the first fifteen minutes after administration..
Under 35 U.S.C. § 271(e)(4)(A), the effective date of any Food and Drug Administration
approval of Actavis' ANDA No. 20-6952 shall be a date not earlier than the later. expiration date
of the '096 and '742 patents, including any extensions and marketing exclusivities (September
12, 2034). Pursuant to 35 U.S.C. § 271(e)(4)(B), the court finds that Actavis, its officers, agents,
attorneys, and employees, and those acting in privity or concert with any of them, should be
enjoined from engaging in the commercial manufacture, use, offer to sell, or sale with the United
States, or importation into the United States of Actavis' ANDA Product prior to the expiration of
the '096 and '742 patents.
In sum, the court finds infringement of all of the asserted claims of the '096 and '742
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