Briefs in Support of Motion To Dismiss For Invalidity Unpatentable Subject Matter Under 35 U.S.C Section 101 Briefs in Endo V Actavis Kidney Function Patent Delaware Case

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 1 of 18 PageID #: 123
IN THE UNITED STATES DISTRICT COURT

FOR THE DISTRICT OF DELAWARE
ENDO PHARMACEUTICALS INC. and
MALLINCKRODT LLC,
Plaintiffs,
v.
ACTAVIS INC. and ACTAVIS SOUTH
ATLANTIC LLC,
Defendants.
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C.A. No. 14-1381-RGA
OPENING BRIEF IN SUPPORT OF

DEFENDANTS MOTION TO DISMISS COUNTS I, III AND IV
OF PLAINTIFFS COMPLAINT PURSUANT TO FED. R. CIV. P. 12(b)(6)
YOUNG CONWAY STARGATT & TAYLOR LLP

Adam W. Poff (No. 3990)
Robert M. Vrana (No. 5666)
Rodney Square
1000 North King Street
Wilmington, DE 19801
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com
OF COUNSEL:
HOLLAND & KNIGHT LLP
Charles Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
charles.weiss@hklaw.com
Dated: January 20, 2015
Attorneys for Defendants Actavis Inc. and

Actavis South Atlantic LLC
TABLE OF CONTENTS
INTRODUCTION .......................................................................................................................... 1
NATURE AND STAGE OF THE PROCEEDINGS ..................................................................... 2
SUMMARY OF THE ARGUMENT ............................................................................................. 3
STATEMENT OF FACTS ............................................................................................................. 4
ARGUMENT .................................................................................................................................. 6
I. The Complaint does not plead sufficient facts to show intent to induce
infringement of the 737 patent........................................................................................... 6
A. Endo has not pled sufficient facts to show that Actaviss future sales of the
pending ANDA product will induce infringement of the 737 patent .......................... 7
B. Endo has not pled sufficient facts to show that Actavis induces infringement
of the 737 patent by selling its already-approved extended-relief
oxymorphone tablets ..................................................................................................... 8
II. The 737 patent is invalid for claiming unpatentable subject matter under 35
U.S.C. 101 ........................................................................................................................ 9
CONCLUSION ............................................................................................................................. 12
TABLE OF AUTHORITIES
Cases
Abbott Labs. v. TorPharm, Inc.,
300 F.3d 1367 (Fed. Cir. 2002)........................................................................................... 7
Artemi Ltd. v. Safe-Strap Co., Inc.,
947 F. Supp. 2d 473 (D.N.J. 2013) ..................................................................................... 9
Ashcroft v. Iqbal,
556 U.S. 662 (2009) ............................................................................................................ 6
AstraZeneca Pharms. LP v. Apotex Corp.,
669 F.3d 1370 (Fed. Cir. 2012)....................................................................................... 6, 7
Bayer Schering Pharma AG v. Lupin, Ltd.,
676 F.3d 1316 (Fed. Cir. 2012)........................................................................................... 8
Bell Atlantic Corp. v. Twombly,
550 U.S. 544 (2007) ........................................................................................................ 6, 9
DSU Medical Corp. v. JMS Co., Ltd.,
471 F.3d 1293 (Fed. Cir. 2006)........................................................................................... 9
Genetic Techs., Ltd. v. Bristol-Myers Squibb Co.,
__ F. Supp. 3d __, 2014 WL 5507637 (D. Del. Oct. 30, 2014) ........................................ 10
Genetic Techs., Ltd. v. Lab. Corp. of Am. Holdings,
Civ. No. 12-1736-LPS-CJB, 2014 WL 4379587 (D. Del. Sept. 3, 2014) ........................ 10
Global-Tech Appliances, Inc. v. SEB S.A.,
131 S. Ct. 2060 (2011) ........................................................................................................ 8
In re Bill of Lading Transmission & Processing Sys. Patent Litig.,
681 F.3d 1323 (Fed. Cir. 2012)........................................................................................... 9
In re Burlington Coat Factory Securities Litig.,
114 F.3d 1410 (3d Cir. 1997).............................................................................................. 6
Mallinckrodt, Inc. v. E-Z-Em Inc.,
670 F. Supp. 2d 349 (D. Del. 2009) .................................................................................... 9
Mayo Collaborative Servs. v. Prometheus Labs., Inc.,
132 S. Ct. 1289 (2012) ........................................................................................ 1, 9, 10, 11
Morrow v. Balaski,
719 F.3d 160 (3d Cir. 2013)................................................................................................ 6
ii
Ricoh Co. v. Quanta Computer Inc.,

550 F.3d 1325 (Fed. Cir. 2008)........................................................................................... 7
Warner-Lambert Co. v. Apotex Corp.,
316 F.3d 1348 (Fed. Cir. 2003)....................................................................................... 6, 7
Xpoint Techs., Inc. v. Microsoft Corp.,
730 F. Supp. 2d 349 (D. Del. 2010) .................................................................................... 9
Statutes
35 U.S.C. 101 ............................................................................................................................... 3
35 U.S.C. 271(a) .......................................................................................................................... 2
35 U.S.C. 271(b) .......................................................................................................................... 6
35 U.S.C. 271(c) ...................................................................................................................... 6, 8
35 U.S.C. 271(e)(2)...................................................................................................................... 2
iii
INTRODUCTION
The complaint of plaintiffs (collectively, Endo) alleges that defendants (collectively,
Actavis) have infringed U.S. Patents 8,808,737 (the 737 patent) and 8,871,779 (the 779
patent) by (i) selling an FDA-approved extended-release formulation of oxymorphone, and (ii)
submitting an Abbreviated New Drug Application (ANDA) seeking FDA approval for a
different formulation of the same drug. Because this is a motion to dismiss under Fed. R. Civ. P.
12(b)(6), the lengthy history of litigation between Endo and Actavis on these products is for now
largely irrelevant, and in the interest of brevity Actavis will dispense with it in this brief.1 With
respect to the current part of that saga, Endo has related cases pending against Actavis in the (i)
Southern District of New York for infringement of other patents allegedly infringed by the same
product and ANDA (Civil Action Nos. 12-08985 and 13-00436), and (ii) District of New Jersey
for false advertising of the commercial product (Civil Action No. 12-07591, on remand from
Endo Pharms. Inc. v. Actavis Inc., No. 13-4096, 2014 WL 6844812 (3d Cir. Dec. 5, 2014)).
Actavis now moves to dismiss Endos claims for infringement of the 737 patent (Counts
I, III, and IV), because (1) the Complaint fails to state a claim for indirect infringement (and
cannot state a claim for direct infringement) and (2) all claims of the 737 patent are invalid for
claiming a law of nature that is unpatentable under 35 U.S.C. 101, namely, the relationship
between bioavailability of oxymorphone and impaired kidney function. See Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012).
Defendants follow the Complaints lead of referring to both defendants collectively as

Actavis, because for present purposes it is not necessary to distinguish between them.
NATURE AND STAGE OF THE PROCEEDINGS

In November 2014, Endo filed its Complaint for patent infringement (D.I. 1). It accuses
one already-marketed product of infringement under 35 U.S.C. 271(a), and accuses a pending
ANDA of infringement under 35 U.S.C. 271(e)(2).
As noted above, both the commercial product and the as-yet-unapproved product that is
the subject of the ANDA are extended-release formulations of oxymorphone.2 Oxymorphone is
a opioid analgesic, and its use in extended-release form is for people who need strong, aroundthe-clock pain relief over lengthy periods of time.
In lieu of filing an Answer, Actavis is moving under Fed. R. Civ. P. 12(b)(6) to dismiss
Endos claims for infringement of the 737 patent (Counts I, III, and IV of the Complaint).
The details of the products are not important for this motion, but the commercial product is
generic to the original formulation of Endos branded product Opana ER, and the pending
ANDA seeks approval of a product generic to the current formulation of Opana ER.
2
SUMMARY OF THE ARGUMENT

1.
Because all claims of the 737 patent are directed to methods of treatment, Actavis can be
liable only for indirect infringement. To state a claim, Endo must plead not just that the products
at issue are capable of use by doctors (or patients) in an infringing manner, but that Actaviss
instructions for use affirmatively direct their use in an infringing manner. As to the stillunapproved product described in Actaviss pending ANDA, the inquiry is limited to the product
label, which does not direct use of the product in the manner claimed by the 737 patent. Endo
has not pled, and cannot plead, that the label directs users (doctors or patients) to infringe.
As to the already-approved commercial product, the legal standard of induced
infringement is same but the permissible inquiry is not automatically limited to the label.
Specifically, although it is highly unusual for manufacturers of generic products to detail their
use to physicians (in the way that manufacturers of branded products detail those products), it is
at least theoretically possible that: (i) if such promotion occurred, and (ii) if that promotion
directed physicians to use the product in a way not described on the label, the generic
manufacturer could be found to induce infringement even if the label itself did not give
directions for that use. But even if such activities are possible in theory, they are implausible in
practice. And most importantly, they are not alleged by Endo in the Complaint.
2.
All claims of Endos 737 patent are invalid because they are directed to unpatentable
subject matter under 35 U.S.C. 101, viz., a law of nature. Specifically, the claims recite the
natural law that the bioavailability of oxymorphone is increased in people with impaired kidney
function, and are not transformed into a patent-eligible process by reciting that doctors should
in dependence on the measurement of kidney function give a lower dosage of drug.
STATEMENT OF FACTS
Claim 1 of the 737 patent is exemplary, and is reproduced below:
1. A method of treating pain in a renally impaired patient, comprising the
steps of:
a. providing a solid oral controlled release dosage form,
comprising:
i. about 5 mg to about 80 mg of oxymorphone or a
pharmaceutically acceptable salt thereof as the sole active
ingredient; and
ii. a controlled release matrix;
b. measuring a creatinine clearance rate of the patient and
determining it to be (a) less than about 30 ml/min, (b) about 30
mL/min to about 50 mL/min, (c) about 51 mL/min to about 80
mL/min, or (d) above about 80 mL/min; and
c. orally administering to said patient, in dependence on which
creatinine clearance rate is found, a lower dosage of the dosage
form to provide pain relief;
wherein after said administration to said patient, the average AUC
of oxymorphone over a 12-hour period is less than about 21
nghr/mL.
737 patent (D.I. 1, Ex. A) at 48:7-26. Dependent claims 2 and 3 specify that the AUC in the
terminal wherein clause is less than about 20 and 19 nghr/mL, respectively.
Independent claim 4 is identical to claim 1, except the final clause reads wherein after
said administration to said patient, the Cmax of oxymorphone is less than about 1.4 ng/mL.
Dependent claims 5 and 6 limit the Cmax to about 1.3 and 1.2 ng/mL, respectively.
Neither of the accused Actavis products (nor Endos branded product Opana ER) are
specially designed or labelled for treatment of pain in people with impaired kidney function.
The only discussion in the labels (of all these products) on this point is (i) information about
increased bioavailability of oxymorphone in people with renal impairment, and (ii) general
4
advice to start with a low dose in people with a creatinine clearance of less than 50 mL/min and
to titrate slowly while monitoring side effects.
2.6 Patients with Renal Impairment
In patients with creatinine clearance rates less than 50 mL/min,
start OPANA ER in the opioid-nave patient with the 5 mg dose.
For patients on prior opioid therapy, start OPANA ER at 50%
lower than the starting dose for a patient with normal renal
function on prior opioids and titrate slowly. Monitor patients
closely for signs of respiratory or central nervous system
depression.
*
8.7 Renal Impairment

Patients with moderate to severe renal impairment were shown to
have an increase in oxymorphone bioavailability ranging from 5765%. Start opioid nave patients with the 5 mg dose of OPANA
ER and titrate slowly while closely monitoring for respiratory and
central nervous system depression. For patients on prior opioid
therapy, start at 50% of the dose for a patient with normal renal
function on prior opioids and titrate slowly.
*
Renal impairment
Data from a pharmacokinetic study involving 24 patients with
renal dysfunction show an increase of 26%, 57%, and 65% in
oxymorphone bioavailability in mild (creatinine clearance 51-80
mL/min; n=8), moderate (creatinine clearance 30-50 mL/min;
n=8), and severe (creatinine clearance <30 mL/min; n=8) patients,
respectively, compared to healthy controls.
Exhibit 1 at 2.6, 8.7, 12.3 (label of Opana ER, parenthetical references omitted); see also
Exhibits 2 and 3 (labels for Actavis commercial product and pending ANDA product,
respectively).3
Exhibits are to the Declaration of Adam Poff in Support of Defendants Motion to Dismiss.
5
ARGUMENT
To survive a motion to dismiss, a complaint must contain sufficient factual matter,
accepted as true, to state a claim to relief that is plausible on its face. Ashcroft v. Iqbal, 556
U.S. 662, 678 (2009). The complaint requires more than labels and conclusion, and a formulaic
recitation of the elements of a cause of action will not do. Bell Atlantic Corp. v. Twombly, 550
U.S. 544, 555 (2007). Unsupported conclusions, unwarranted inferences, and legal conclusions
phrased as factual allegations also are not accepted as true for the purposes of a Rule 12(b)(6)
motion. See Morrow v. Balaski, 719 F.3d 160, 165 (3d Cir. 2013) ([W]e are not compelled to
accept unsupported conclusions and unwarranted inferences, or a legal conclusion couched as a
factual allegation.).
In ruling on motions to dismiss, courts may examine documents integral to or explicitly
relied upon in the complaint. In re Burlington Coat Factory Securities Litig., 114 F.3d 1410,
1426 (3d Cir. 1997). In ANDA cases, the applicants submissions to the FDA are in this
category. See AstraZeneca Pharms. LP v. Apotex Corp., 669 F.3d 1370, 1378 n.5 (Fed. Cir.
2012).
I.
The Complaint does not plead sufficient facts to show intent to induce infringement
of the 737 patent
Because the 737 patent is directed to methods of treatment, the Complaint does not
suggest that Actavis has practiced or will practice the claimed method. See Warner-Lambert Co.
v. Apotex Corp., 316 F.3d 1348, 1363 (Fed. Cir. 2003) (no direct infringement by drug
manufacturer where patent is to method of treatment). Thus, Endos claim must be based on
induced infringement under 35 U.S.C. 271(b) or contributory infringement under 35 U.S.C.
271(c). See id. When as here the accused product has substantial noninfringing uses, intent to
induce infringement requires not simply knowledge that it may be put to infringing uses, but
6
statements or actions directed to promoting infringement. Ricoh Co. v. Quanta Computer Inc.,
550 F.3d 1325, 1341 (Fed. Cir. 2008).
A.
Endo has not pled sufficient facts to show that Actaviss future sales of the
pending ANDA product will induce infringement of the 737 patent
For method-of-treatment claims like those in the 737 patent, an applicants submission
of an ANDA can be found to induce infringement only if it seeks approval to market the drug for
the patented use. See AstraZeneca, 669 F.3d at 1379; Warner-Lambert, 316 F.3d at 1354-55.
Because drug manufacturers are bound by strict statutory provisions to sell only those products
that comport with the ANDAs description of the drug, an ANDA specification defining a
proposed generic drug in a manner that directly addresses the issue of infringement will control
the infringement inquiry. Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002).
Here, the proposed label in the ANDA (Exhibit 3) does not direct physicians (or anyone
else) to practice any claim of the 737 patent. Claim 1, which is representative, requires in part
(i) measuring a persons creatinine clearance, (ii) determining if it is less than about 30 ml/min,
about 30 to about 50 mL/min, about to about 80 mL/min, or above about 80 mL/min, and (iii)
orally administering to the patient in dependence on which creatinine clearance rate is found, a
lower dosage of drug to provide pain relief. Nothing on the label directs doctors to perform any
of these steps, and inducement would require that it direct the physician to perform all of them.
First, the label does not direct doctors to measure the creatinine clearance at all. Second,
even if the creatinine clearance is measured, the label does not direct the doctor to determine if
it falls within one of the four specified ranges. Third, it does not direct administration of a lower
dose in dependence on which of the four ranges contains the measured creatinine clearance
rate. Fourth, it does not direct giving a lower dose correlating to the four ranges to provide
pain relief, but instead speaks only to monitoring side effects. Cf. Bayer Schering Pharma AG
7
v. Lupin, Ltd., 676 F.3d 1316, 1322-24 (Fed. Cir. 2012) (statements in label providing
information on pharmacokinetics of a drug are not directions to infringe).
Endos claim for contributory infringement similarly fails. There is no factual allegation
that the product is especially made or especially adapted for use in an infringement, and it is
also plain on the face of the label that the product is suitable for substantial noninfringing use.
35 U.S.C. 271(c). See also Global-Tech Appliances, Inc. v. SEB S.A., 131 S. Ct. 2060, 2068
(2011) (contributory infringement under section 271(c) requires knowledge that the product will
be used to infringe).
Accordingly, the Complaint fails to state a claim that commercial manufacture and sale of
the proposed ANDA product with the label information submitted to the FDA for approval
would infringe. Counts III and IV must be dismissed.
B.
Endo has not pled sufficient facts to show that Actavis induces infringement
of the 737 patent by selling its already-approved extended-relief
oxymorphone tablets
The label for Actaviss currently sold extended-release oxymorphone tablets (Exhibit 3)
contains the same language regarding impaired kidney function as does the label for the
proposed ANDA product. For the same reasons, Endo does not and cannot plead a claim for
infringement based on the label itself.
Nor has Endo pled facts outside the label that would demonstrate indirect infringement.
As noted above, it is at least theoretically possible in the case of a marketed product that the
manufacturer could induce infringement by promoting (off-label) infringing uses. The question
of whether allegations to that effect are sufficiently plausible is not at issue, because Endo has
pled no facts to that effect. The only fact pled by Endo regarding the existing product is that
Actavis sells it (Complaint 29-33).
But to survive a motion to dismiss, the Complaint must contain facts plausibly showing
that [defendants] specifically intended their customers to infringe [the 737 patent] and knew that
the customers acts constituted infringement. In re Bill of Lading Transmission & Processing
Sys. Patent Litig., 681 F.3d 1323, 1339 (Fed. Cir. 2012). Induced infringement requires
purposeful, culpable expression and conduct. DSU Medical Corp. v. JMS Co., Ltd., 471 F.3d
1293, 1306 (Fed. Cir. 2006). A complaint that merely recites the elements for indirect
infringement is insufficient to state a claim. See Xpoint Techs., Inc. v. Microsoft Corp., 730 F.
Supp. 2d 349, 357 (D. Del. 2010); Mallinckrodt, Inc. v. E-Z-Em Inc., 670 F. Supp. 2d 349, 354
(D. Del. 2009); Artemi Ltd. v. Safe-Strap Co., Inc., 947 F. Supp. 2d 473, 480 (D.N.J. 2013).
Here, the only statement in the Complaint regarding induced infringement of the 737
patent is a legal conclusion that Actaviss sale of the accused product induces infringement:
37.
Actaviss commercial manufacture, offer for sale, or sale of
its Generic Oxymorphone ER Tablets infringe the 737 Patent
under 35 U.S.C. 271(a)-(c), including without limitation that it
induces physicians and patients to infringe the 737 Patent by
performing all of the recited steps of one or more of claims 1 6 of
the 737 Patent.
Complaint 37. Unlike well-pled and plausible facts, which generally must be taken as true on a
motion to dismiss, legal conclusions such as this have no weight and do not carry Endos burden
to state a claim for indirect infringement. Twombly, 550 U.S. at 555. Thus, Count I must be
dismissed.
II.
The 737 patent is invalid for claiming unpatentable subject matter under 35 U.S.C.
101
In Mayo, the Supreme Court held invalid a method of treatment claim highly analogous
to the claims of the 737 patent for claiming unpatentable subject matter because the method of
treatment claimed did nothing more than state a natural law governing the effects of a certain
drug on the human body and add routine and conventional treatment steps by a physician.
9
Following Mayo, the District of Delaware has repeatedly dismissed similar claims as invalid at
the pleading stage for claiming similar unpatentable subject matter. See, e.g., Genetic Techs.,
Ltd. v. Bristol-Myers Squibb Co., __ F. Supp. 3d __, 2014 WL 5507637, *6-*12 (D. Del. Oct. 30,
2014) (method of analyzing and amplifying natural variations in non-coding DNA held invalid
on motion to dismiss); Genetic Techs., Ltd. v. Lab. Corp. of Am. Holdings, Civ. No. 12-1736LPS-CJB, 2014 WL 4379587, *10-*14 (D. Del. Sept. 3, 2014) (method of analyzing DNA to
predict athletic performance held invalid on motion to dismiss).
The claim language held invalid in Mayo is provided in the table below comparing that
language to exemplary Claim 1 of the 737 patent:
Claim 1 of the patent held invalid in Mayo
132 S. Ct. at 1295
Claim 1 of the 737 patent
1. A method of optimizing therapeutic efficacy

for treatment of an immune-mediated
gastrointestinal disorder, comprising:
1. A method of treating pain in a renally

impaired patient, comprising the steps of:
(a) administering a drug providing 6thioguanine to a subject having said immunemediated gastrointestinal disorder; and
a. providing a solid oral controlled release

dosage form, comprising: i. about 5 mg to
about 80 mg of oxymorphone or a
pharmaceutically acceptable salt thereof as the
sole active ingredient; and ii. a controlled
release matrix;
(b) determining the level of 6-thioguanine in

said subject having said immune-mediated
gastrointestinal disorder,
b. measuring a creatinine clearance rate of the

patient and determining it to be (a) less than
about 30 ml/min, (b) about 30 mL/min to about
50 mL/min, (c) about 51 mL/min to about 80
c. orally administering to said patient, in
dependence on which creatinine clearance rate
is found, a lower dosage of the dosage form to
provide pain relief;
wherein the level of 6-thioguaninine less than

about 230 pmol per 8x108 red blood cells
indicates a need to increase the amount of said
drug subsequently administered to said subject
wherein after said administration to said

patient, the average AUC of oxymorphone
over a 12-hour period is less than about 21
10
and
nghr/mL.
wherein the level of 6-thioguaninine greater

than about 400 pmol per 8x108 red blood cells
indicates a need to decrease the amount of said
drug subsequently administered to said subject.
In analyzing the claim in Mayo, the Supreme Court observed that the patent sets forth a
law of nature, namely, relationships between concentrations of certain metabolites in the blood
and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm. 132
S. Ct. at 1296. Such relationships are natural laws because they are a consequence of the ways in
which drugs are metabolized, which are entirely natural processes. Id. at 1297. To become
patent eligible, the claims would have to add enough to the law of nature to qualify as a patenteligible process that applies natural laws. Id.
The Supreme Court held that the additional steps in Mayo did not add enough to confer
patentability. It held that the administering step did nothing more than limit the relevant
audience to doctors who treat patients with certain diseases with thiopurine drugs, and that
merely limiting a natural law to a particular technological environment did not render the claim
patent-eligible. Id. at 1297. The wherein clauses simply told the doctor what the relevant
natural laws were, at most suggesting that doctors take the laws into account when treating
patients. Id. And the determining step tells the doctor to determine the level of the relevant
metabolites in the blood. Id. Because the patents stated that such methods were well-known in
the art, the determining step was conventional pre-solution activity that did not apply the law
of nature in a way to create a patent-eligible process. Id. at 1298.
The 737 patent has many of the same flaws. As in Mayo, the 737 patent states a natural
law: the bioavailability of oxymorphone is increased in patients with renal impairment. Indeed,
it describes the invention using that exact language. D.I. 1, Ex. A at Abstract.
11
The claims other steps are a providing step, a measuring/determining step, and an
administering step. The providing and administering steps, like the administering step
in Mayo, simply defines the audience, and the patent states that (i) extended-release
oxymorphone was already on the market (D.I. 1, Ex. A at 3:40-49), and that oxymorphone is
widely used in the treatment of acute and chronic pain. Id. at 1:19-22.
The measuring/determining step tells the doctor to measure the patients creatinine
level to determine the severity of renal impairment, but the specification necessarily describes
this as a known method. D.I. 1, Ex. A at 28:4-11, 28:61-29:15. Like the determining step in
Mayo, this is just routine pre-solution activity using well-known methods to gather the
information needed to apply the natural law.
None of these infirmities illustrated with respect to exemplary Claim 1 is eliminated by
elements of the remaining claims, and thus they fall together with Claim 1 for the same reason.
CONCLUSION
For the foregoing reasons, Actavis respectfully urges the Court to grant its motion and
dismiss Counts I, III, and IV of the Complaint.
YOUNG CONAWAY STARGATT &
TAYLOR, LLP
Of Counsel:
Charles Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
/s/ Adam W. Poff

Rodney Square
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com

12
CERTIFICATE OF SERVICE
I, Adam W. Poff, hereby certify that on January 20, 2015, I caused to be electronically
filed a true and correct copy of the foregoing document with the Clerk of the Court using
CM/ECF, which will send notification that such filing is available for viewing and downloading
to the following counsel of record:
Jack B. Blumenfeld, Esquire
Julia Heaney, Esquire
Morris Nichols Arsht & Tunnell LLP
1201 North Market Street
P.O. Box 1347
Wilmington, DE 19899-1347
jblumenfeld@mnat.com
jheaney@mnat.com
Attorneys for Plaintiffs
I further certify that on January 20, 2015, I caused a copy of the foregoing document
to be served by e-mail on the above-listed counsel and on the following:
Jonathan D.J. Loeb, Esquire
Dechert LLP
2440 W. El Camino Real
Suite 700
Mountain View, CA 94040
jonathan.loeb@dechert.com
Martin J. Black, Esquire
Dechert LLP
Circa Centre
2929 Arch Street
Philadelphia, PA 19104
martin.black@dechert.com
Robert D. Rhoad, Esquire
Dechert LLP
902 Carnegie Center
Suite 500
Princeton, NJ 08540
robert.rhoad@dechert.com
01:16529567.1

TAYLOR, LLP
/s/ Adam W. Poff
Robert M. Vrana (No. (5666)
Rodney Square
1000 N. King Street
Wilmington, Delaware 19801
apoff@ycst.com
Attorneys for Defendants
2
01:16529567.1

MALLINCKRODT LLC,
Plaintiffs,
v.
ATLANTIC LLC,
Defendants.
)
)
)
)
)
)
)
)
)
)
)
C.A. No. 14-1381-RGA
REPLY BRIEF IN FURTHER SUPPORT OF

DEFENDANTS MOTION TO DISMISS COUNTS I, III AND IV
OF PLAINTIFFS COMPLAINT PURSUANT TO FED. R. CIV. P. 12(b)(6)

Rodney Square
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com
OF COUNSEL:
Charles Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
Dated: March 23, 2015

TABLE OF CONTENTS
INTRODUCTION .......................................................................................................................... 1
ARGUMENT .................................................................................................................................. 2
I. ENDO CANNOT SUSTAIN A CLAIM FOR INFRINGEMENT ON THE
PLEADINGS ...................................................................................................................... 2
A. The acts that Actavis has taken, as pled by Endo, cannot constitute
inducement to infringe the 737 patent ......................................................................... 2
B. Mere notice of Endos claims is insufficient to survive this motion to dismiss ........... 4
II. THE 737 PATENT IS INVALID FOR CLAIMING AN UNPATENTABLE
LAW OF NATURE ............................................................................................................ 5
A. Endos argument for induced infringement precisely illustrates why the 737
patent is directed to unpatentable subject matter .......................................................... 5
B. Straightforward application of the Mayo/Alice two-part test shows the 737
patent to claim unpatentable subject matter .................................................................. 7
CONCLUSION ............................................................................................................................. 10
Cases
Abbott Labs. v. TorPharm, Inc.,
300 F.3d 1367 (Fed. Cir. 2002)........................................................................................... 3
Alice Corp. Pty, Ltd. v. CLS Bank Intl,
134 S. Ct. 2347 (2014) ........................................................................................................ 7
AstraZeneca LP v. Apotex, Inc.,
633 F.3d 1042 (Fed. Cir. 2010)........................................................................................... 4
AstraZeneca Pharms. LP v. Apotex Corp.,
669 F.3d 1370 (Fed. Cir. 2012)....................................................................................... 3, 5
Classen Immunotherapies, Inc. v. Biogen IDEC,
659 F.3d 1057 (Fed. Cir. 2011)........................................................................................... 8
No. WDQ-04-2607, 2012 WL 3264941 (D. Md. Aug. 9, 2012) ........................................ 9
Gottschalk v. Benson,
409 U.S. 63 (1972) .............................................................................................................. 7
In re Bill of Lading Transmission & Processing Sys. Patent Litig.,
681 F.3d 1323 (Fed. Cir. 2012)........................................................................................... 5
Lucent Techs., Inc. v. Gateway, Inc.,
580 F.3d 1301 (Fed. Cir. 2009)........................................................................................... 2
132 S. Ct. 1289 (2012) ............................................................................................... passim
Mirror World, LLC v. Apple Inc.,
692 F.3d 1351 (Fed. Cir. 2012)........................................................................................... 3
MONEC Holding AG v. Motorola Mobility, Inc.,
897 F. Supp. 2d 225 (D. Del. 2012) .................................................................................... 5
Simon v. FIA Card Servs., N.A.,
732 F.3d 259 (3d Cir. 2013)................................................................................................ 5
Warner-Lambert Co. v. Apotex Corp.,
316 F.3d 1348 (Fed. Cir. 2003)....................................................................................... 2, 3
Statutes
35 U.S.C. 101 ............................................................................................................................... 7
ii
INTRODUCTION
Endo cannot state a claim for induced infringement of U.S. Patent No. 8,808,737 (the
737 Patent) against Actavis because it cannot point to specific language in Actaviss product
label directing physicians to infringe the claims. The 737 patents claims require physicians to
measure a patients creatinine clearance level (an indication of kidney function), determine
which of four specified ranges it falls into, and administer a lower dose of oxymorphone to the
patient in dependence on the measured level such that the concentration of oxymorphone in the
patients blood remains under a particular number. The language of Actaviss product labels,
which do nothing more than instruct physicians to reduce the dose of oxymorphone in renally
impaired patients and inform them of a clinical study, cannot induce infringement of each
limitation of these claims.
Endos claims related to the 737 patent should also be dismissed because the 737
patents addition of a step to administer oxymorphone for pain relief, a step described in the
patents own specification as having been known in the art for decades, is trivial post-solution
activity that does not render claims patentable. A patent could not simply recite a law of nature
and then add the instruction apply the law. Mayo Collaborative Servs. v. Prometheus Labs.,
Inc., 132 S. Ct. 1289, 1297 (2012). Not only does the 737 patent do nothing more than that, but
Endo argues that Actavis induces infringement by doing nothing more than telling doctors the
law of nature; Endo cannot even argue that Actavis has instructed doctors to apply it. This is not
to say that no method of treatment patent is patentable, simply that a claim to a law of nature
here, as Endo freely admits, a discovered relationship between bioavailabity of oxymorphone
and level of renal impairment (D.I. 18 (Opp. Br.) at 14)cannot be made patentable by adding
an administering step that is common knowledge within the relevant art and confirmed to be
common knowledge within the asserted patent itself.
1
ARGUMENT
I.
ENDO CANNOT SUSTAIN A CLAIM FOR INFRINGEMENT ON THE

PLEADINGS
A.
The acts that Actavis has taken, as pled by Endo, cannot constitute
inducement to infringe the 737 patent
Endo cannot show that the label for either of Actaviss products instructs physicians to
practice every limitation of a claim of the 737 patent. The 737 patents claims require a
physician to perform a series of specific steps:
(1)
providing a solid oral controlled release dosage of oxymorphone

from about 5 mg to about 80 mg in a controlled release matrix;
(2)
measuring a creatinine clearance rate of a patient;
(3)
determining that rate to be within one of four ranges (which

correspond to a patients level of renal impairment);
(4)
administering a lower dosage of oxymorphone in dependence on

which creatinine clearance rate is found, such that
(5)
after administration, either the average area-under-curve or

maximum concentration of oxymorphone is less than a specified
number (which varies between the six patent claims).
D.I. 12 (Opening Br.) at 4; D.I. 1, Ex. A at 48:7-26. In its opposition brief, Endo fails to identify
language in Actaviss labels instructing a physician to follow these steps; it only points generally
to language instructing a physician to reduce the dose in patients with renal impairment. D.I.
18 at 9-10.
In order to show inducement, Endo would have to show that Actaviss product labels
instruct physicians to perform every limitation of a patented claim. See Warner-Lambert Co. v.
Apotex Corp., 316 F.3d 1348, 1363 (Fed. Cir. 2003) (Inducement requires proof that the
accused infringer knowingly aided and abetted anothers direct infringement of the patent.);
Lucent Techs., Inc. v. Gateway, Inc., 580 F.3d 1301, 1317 (Fed. Cir. 2009) (To infringe a
method claim, a person must have practiced all steps of the claimed method.). Its failure to
identify such language is dispositive.
In particular, an ANDA applicant cannot be liable for induced infringement of a method
of treatment patent where the product label does not direct a physician to perform each step of
the patented method. AstraZeneca Pharms. LP v. Apotex Corp., 669 F.3d 1370, 1379 (Fed. Cir.
2012) (AstraZeneca II); Warner-Lambert, 316 F.3d at 1354-55. Endos suggestion that these
cases only apply to ANDAs for a different indication from the patented method, D.I. 18 at 1112, is incorrect. The question, per the Court in AstraZeneca II, is whether a use listed in the
ANDA or on the proposed label is claimed in a patent. 669 F.3d at 1378. The use claimed by
the 737 patent is not merely the administration of oxymorphone for pain relief; the patent freely
admits that oxymorphone was widely used in the treatment of acute and chronic pain in the
prior art. D.I. 1, Ex. A at 1:19-22.
Moreover, even if Endo could somehow find suggestion to perform each step of a claim
somewhere in Actaviss label, the possibility that a physician could cobble together separate
instructions in a label to infringe a method claim is insufficient to show inducement. In Mirror
World, LLC v. Apple Inc., 692 F.3d 1351, 1360 (Fed. Cir. 2012), the court affirmed judgment as
a matter of law of no induced infringement where the only evidence of inducement came from
the defendants user manuals containing instructions in separate places, not connected to each
other, to perform the steps claimed by the patent. When manuals only teach customers each
step of the claimed method in isolation, but not all the steps of the claimed method together,
the manuals alone cannot support infringement. Id. Here, Endo relies on Actaviss labels alone
to show inducementit is forced to rely on the label alone for the ANDA product, Abbott Labs.
v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002), and has pled no other factual
allegations to show inducement for the already-approved extended-release oxymorphone tablets.

D.I. 12 (Opening Br.) at 8-9. The possibility that a physician could theoretically combine
instructions scattered throughout the labele.g., advice to reduce the dose in patients with
renal impairment, direction from another section to initiate the dosing regimen for each patient
individually, direction from another section to start at a dose of 50% and titrate slowly, and
information in section 12.3 about a study comparing bioavailability of oxymorphone to
creatinine clearance rates (D.I. 18 at 9-10)does not show inducement as a matter of law.
Endos reliance on AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042 (Fed. Cir. 2010)
(AstraZeneca I), fails because the patent in that case, unlike the patent here, was broad enough
to encompass the language in the product label. The representative claim of the patent in that
suit was simply: A method of treating a patient suffering from a respiratory disease, the method
comprising administering to the patient a nebulized dose of a budesonide composition in a
continuing regimen at a frequency of not more than once per day. Id. at 1048. The court found
that the labels instruction to titrate down from a twice-daily dose would induce infringement
because the only way a physician could reduce the dosage was to administer the drug once-daily
and therefore infringe. Id. at 1057. No such inferred instruction to perform the steps of the 737
patent can be found in Actaviss product label, as merely reducing a dose slowly cannot instruct
a physician to perform the precise measuring, determining, and administering a lower dose
dependent on level of renal impairment required by the 737 patent.
B.
Mere notice of Endos claims is insufficient to survive this motion to dismiss
The fact that Endos Complaint identifies the specific infringing acts, the entity that
actively induces infringement (Actavis), and the people it is inducing to infringe (D.I. 18 at 9)
does not immunize the Complaint from a Rule 12(b)(6) motion to dismiss. A Rule 12(b)(6)
motion to dismiss may be granted if, accepting the well-pleaded allegations in the complaint as
4
true and viewing them in the light most favorable to the plaintiff, a court concludes that those
allegations could not raise a claim of entitlement to relief. Simon v. FIA Card Servs., N.A.,
732 F.3d 259 (3d Cir. 2013); MONEC Holding AG v. Motorola Mobility, Inc., 897 F. Supp. 2d
225, 234-35 (D. Del. 2012) (dismissal of induced infringement claim for failure to allege facts
necessary to show intent). Endos Complaint as to the 737 Patent fails not because it failed to
provide enough factual detail, but because the details Endo provided, taken as true, are
insufficient to plausibly demonstrate that Actavis will induce infringement through selling its
ANDA product or has induced infringement through selling its already-sold extended-release
oxymorphone tablets. A claim for indirect patent infringement can be dismissed on a Rule
12(b)(6) motion if the facts pled by the complaint are inadequate to state a claim for indirect
infringement, as they do here. See In re Bill of Lading Transmission & Processing Sys. Patent
Litig., 681 F.3d 1323, 1338-39 (Fed. Cir. 2012) (affirming dismissal of contributory infringement
because complaint identified substantial non-infringing uses); AstraZeneca II, 669 F.3d at 1379
(affirming dismissal of induced infringement in ANDA case because ANDA was submitted only
for noninfringing use).
II.
THE 737 PATENT IS INVALID FOR CLAIMING AN UNPATENTABLE LAW

OF NATURE
A.
Endos argument for induced infringement precisely illustrates why the 737
patent is directed to unpatentable subject matter
The Court in Mayo explained that a patent that states a law of nature does not become
patentable simply by adding a limitation instructing to apply that law of nature:
A patent [] could not simply recite a law of nature and then add the
instruction apply the law. Einstein, we assume, could not have
patented his famous law by claiming a process consisting of simply
telling linear accelerator operators to refer to the law to determine
how much energy an amount of mass has produced (or vice versa).
Nor could Archimedes have secured a patent for his famous
principle of flotation by claiming a process consisting of simply
5
telling boat builders to refer to that principle in order to determine

whether an object will float.
132 S. Ct. at 1297.
Endo is forced to argue, however, that Actavis induced infringement by telling doctors
about a law of nature and advising them to apply the law. Endo attempts to preclude Actavis
from informing doctors about a useful law of natureexactly the type of activity the courts
intended to allow through the judicially-created rule that laws of nature, natural phenomena, and
abstract ideas are not patentable. The Court in Mayo explained that even a claim tied to a narrow
law of nature, such as the relationship between measured drug levels and treatment protocol,
preempts use and further research into that basic law of nature:
The laws of nature at issue here are narrow laws that may have
limited applications, but the patent claims that embody them
nonetheless implicate this concern [that it will inhibit future
innovation]. They tell a treating doctor to measure metabolite
levels and to consider the resulting measurements in light of the
statistical relationships they describe. In doing so, they tie up the
doctors subsequent treatment decision whether that treatment
does, or does not, change in light of the inference he has drawn
using the correlations. And they threaten to inhibit the
development of more refined treatment recommendations . . . that
combine [the patentees] correlations with later discovered features
of metabolites, human physiology or individual patient
characteristics.
132 S. Ct. at 1302. Endo, to show induced infringement, is forced to argue that Actavis may not
tell doctors about a discovered law of nature, and that doctors may not make treatment decisions
based on that law of nature. Oxymorphone is an old drug, and doctors have treated and will
continue to treat patients for pain relief by giving them oxymorphone. Endos induced
infringement claim does exactly what the Court cautioned against in Mayo: it ties up doctors
treatment decisions by forbidding Actavis from informing of them of the results of a clinical
study, and it inhibits the development of any other treatment recommendation that might be
6
developed as a result of that study. As a result, Endos patent cannot possibly be directed to
patent-eligible subject matter.
B.
Straightforward application of the Mayo/Alice two-part test shows the 737

patent to claim unpatentable subject matter
Endos argument suggests that all method of treatment claims meet the requirements of
35 U.S.C. 101, because any administering step is an application of a law of nature. D.I. 18 at
14. This is not the law under Mayo, 132 S. Ct. 1289, and Alice Corp. Pty, Ltd. v. CLS Bank Intl,
134 S. Ct. 2347 (2014).
Alice Corp., quoting Mayo, sets forth a two step framework for determining whether a
claim is patent-eligible. 134 S. Ct. at 2355. The first step is to determine whether the claims at
issue are directed to a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or
abstract idea. Id. The second step, if the claim is directed to a patent-ineligible concept, is to
search for an inventive concepti.e., an element or combination of elements that is sufficient
to ensure that the patent in practice amounts to significantly more than a patent upon the
[ineligible concept] itself. Id.
Endo effectively concedes the first step of the analysis. Endo writes, it is true that the
claimed inventions relate to the unexpected discovery that the bioavailability of oxymorphone is
increased in patients with renal impairment. D.I. 18 at 14. But Phenomena of nature, though
just discovered . . . are not patentable, as they are the basic tools of scientific and technological
work. Gottschalk v. Benson, 409 U.S. 63, 67 (1972). Endos suggestion that the first step of
analysis should consider the patent to be a method of treating pain in renally impaired patients
by decreasing the dosage of oxymorphone (D.I. 18 at 19) is contradicted by Supreme Court
precedent and by Endos own statements in its brief and in its patent, and by Supreme Court
precedent. As noted above, Endo conceded that the inventions relate to the discovery of the
7
relationship between bioavailability of oxymorphone and level of renal impairment, not to the
development of a novel method of treatment. D.I. 18 at 14. The patent itself explains that
oxymorphone was already widely used for pain relief (D.I. 1, Ex. A at 1:19-23), so the
administration of oxymorphone is not the invention. Rather, the purported discovery of the
relationship between bioavailability of oxymorphone and level of renal impairmentdescribed
in extensive detail in the patent (D.I. 1, Ex. A at 27:59-46:46), and summarized under the
heading CONCLUSION, (D.I. 1, Ex. A at 46:50-57)is the concept that is the subject of the
patent. That relationship, a consequence of the ways in which [oxymorphone is] metabolized
by the body, is an unpatentable law of nature. Mayo, 132 S. Ct. at 1296-97.1
The second step of the Mayo/Alice test is to determine whether the claims add enough to
their statements of the correlations to allow the processes they describe to qualify as patenteligible processes that apply natural laws. Mayo, 132 S. Ct. at 1297 (emphasis in original).
Endos reference to the Classen series of cases in contrast to Mayo supports, rather than defeats,
Actaviss argument for invalidity. Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d
1057 (Fed. Cir. 2011) (Classen I), heavily cited by Endo, is not governing law to the extent it
conflicts with the later Supreme Court decision in Mayo. When the District of Maryland, on
remand from the Federal Circuits vacation of its dismissal in Classen I, reexamined the section
101 issues in light of Mayo, it distinguished Mayo on the ground that the administering steps in
Mayo, unlike the administering steps in Classen, were stated by the patent itself to be wellunderstood, routine activity:
It is this distinctionthat the 737 patent does nothing more than tell doctors to use a natural
law to adjust their use of a common drug for its well-known purposethat avoids Endos
slippery slope argument that Actaviss position would lead to invalidation of all method-oftreatment patents. (D.I. 18 at 19).
8
In [Mayo], the patent acknowledged that scientists routinely

measured metabolites as part of their investigations into the
relationships between metabolite levels and efficacy and toxicity of
thiopurine compounds. The Supreme Court was thus able to
conclude that the steps involved well-understood, routine,
conventional activity previously engaged in by scientists who work
in the field. There is no information in the record here that allows
the Court, on a motion to dismiss for failure to state a claim, to
conclude that the Classen patent claims involve well-understood,
routine, [or] conventional activity.
Classen Immunotherapies, Inc. v. Biogen IDEC, No. WDQ-04-2607, 2012 WL 3264941 at *4
(D. Md. Aug. 9, 2012) (Classen II). Like in Mayo and unlike in Classen II, the 737 patent
here acknowledged that the administration of oxymorphone for pain relief is well-understood,
routine, conventional activity. D.I. 1, Ex. A at 1:19-23. Endos supposedly new treatment
regimen for renally-impaired patients (D.I. 18 at 20) does nothing more than administer
oxymorphone for pain in a conventional way, and instruct doctors to use a natural law to adjust
the dosage. Accordingly, the administering step cannot save the 737 patent. Endo does not
argue that any other step of the 737 patent converts the patent-ineligible discovery of low
bioavailability of oxymorphone in renally impaired patients into a patent-eligible application.
D.I. 18 at 16.
Endos attempt to distinguish Mayo fails, and Mayo still corresponds directly to the claim
limitations of the 737 patent. Endo incorrectly argues that the Mayo claim is different from the
737 patent claim because the Mayo claim administers a drug in order to measure the resulting
metabolite, but the 737 patent claim administers a drug to provide safe and effective pain
relief. D.I. 18 at 16-20. The Mayo claim in fact specified that the drug is used for treatment of
an immune-mediated gastrointestinal disorder. 132 S. Ct. at 1232. The Mayo claim is simply to
administer the drug to a patient, measure the level of metabolite, and adjust the dosage
accordingly to optimize treatment effectiveness. Id. The only conceptual difference between
9
this and the 737 patent claim is that the 737 patent claim suggests that the doctor should adjust
the dosage based on measurement of a different quantity than the concentration of the
administered drug (while specifying that the concentration of the administered drug should
remain below a certain level).
CONCLUSION
For the foregoing reasons and those in Actaviss opening brief, Actavis respectfully urges
the Court to grant its motion and dismiss Counts I, III, and IV of the Complaint.
TAYLOR, LLP
Of Counsel:
Charles Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
/s/ Robert M. Vrana

Rodney Square
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com

01:16841669.1
10
I, Robert M. Vrana, hereby certify that on March 23, 2015, I caused to be electronically
Julia Heaney, Esquire
P.O. Box 1347
jheaney@mnat.com
I further certify that on March 23, 2015, I caused a copy of the foregoing document
Dechert LLP
Suite 700
Dechert LLP
Circa Centre
2929 Arch Street
01:16841743.1

Brian Goldberg, Esquire
Dechert LLP
902 Carnegie Center, Suite 500
Princeton, NJ 08540
brian.goldberg@dechert.com
Blake B. Greene, Esquire
Dechert LLP
300 W. 6th Street, Suite 2010
Austin, TX 78701
blake.greene@dechert.com
Attorneys for Plaintiff Endo Pharmaceuticals Inc.
Jeffrey J. Toney, Esquire
Marcus A. Barber, Esquire
Kasowitz, Benson, Torres & Friedman LLP
333 Twin Dolphin Drive, Suite 200
Redwood Shores, CA 94065
jtoney@kasowitz.com
mbarber@kasowitz.com
Rodney R. Miller, Esquire
Paul G. Williams, Esquire
1349 W. Peachtree Street, N.W., Suite 1500
Atlanta, GA 30309
rmiller@kasowitz.com
pwilliams@kasowitz.com
Attorneys for Plaintiff Mallinckrodt LLC
TAYLOR, LLP
/s/ Robert M. Vrana

Rodney Square
1000 N. King Street
rvrana@ycst.com
2
01:16841743.1


MALLINCKRODT LLC,
Plaintiffs,
v.
ATLANTIC LLC,
Defendants.
)
)
)
)
)
)
)
)
)
)
)
)
)
C.A. No. 14-1381-RGA
ACTAVISS RESPONSE TO ENDOS OBJECTIONS

TO THE REPORT AND RECOMMENDATION
REGARDING DISMISSAL UNDER 35 U.S.C. 101

Rodney Square
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com
OF COUNSEL:
Charles Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
Dated: October 30, 2015

TABLE OF CONTENTS
Page
INTRODUCTION .......................................................................................................................... 1
FACTUAL BACKGROUND ......................................................................................................... 1
ARGUMENT .................................................................................................................................. 2
I.
II.
The R&R correctly concluded that the 737 patents claims were invalid as
claiming an unpatentable law of nature .............................................................................. 2
A.
The 737 patents claims are directed to the law of nature that
bioavailability of oxymorphone is increased in patients with renal
impairment .............................................................................................................. 3
B.
The R&R correctly concluded that nothing in the 737 patents claims
transforms them into patent-eligible subject matter................................................ 4
C.
The R&R correctly found that the 737 patent claims would preempt
future inventions and discoveries in the field ......................................................... 6
D.
The R&Rs reasoning would not lead to invalidation of all method-oftreatment patents ..................................................................................................... 8
If the Court finds that the R&R is in error, the Court should remand Actaviss
motion to dismiss to the Magistrate Judge for further consideration of the alternate
ground of no induced infringement..................................................................................... 8
CONCLUSION ............................................................................................................................... 9
Page(s)
CASES
Alice Corp. Pty. Ltd. v. CLS Bank Intern.,
134 S. Ct. 2347 (2014) ...................................................................................................1, 2, 5, 6
659 F.3d 1057 (Fed. Cir. 2011)..................................................................................................5
Civ. No. WDQ-04-2607, 2012 WL 326491 (D. Md. Aug. 9, 2012) .........................................6
132 S. Ct. 1289 (2012) ..................................................................................................... passim
STATUTES
35 U.S.C. 101 ................................................................................................................................1
ii
INTRODUCTION
The Magistrate Judge correctly applied clear Supreme Court precedent in finding in her
Report and Recommendation (R&R) that Counts I, III, and IV of Endos Complaint regarding
U.S. Patent No. 8,808,737 (the 737 patent) should be dismissed for failure to state a claim
because the 737 patent claims unpatentable subject matter under 35 U.S.C. 101. The Supreme
Court in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1297 (2012),
held that a patent could not simply recite a law of nature and then add the instruction apply the
law. Endos objections to the R&R are inconsistent with clear Supreme Court precedent by
arguing that an instruction to apply a law of naturewhich here is taking account of kidney
function in administering an old drug for an old purposerenders patentable natural laws. But
patent eligibility should not depend simply on the draftmans art. Alice Corp. Pty. Ltd. v. CLS
Bank Intern., 134 S. Ct. 2347, 2359 (2014). The 737 patent does not avoid invalidity simply
because Endo included in the claims an administering step that is a trivial addition to the exact
type of subject matter held unpatentable in Mayo, which claimed using a measurement of blood
levels to indicate a need to decrease the amount of said drug subsequently administered.
FACTUAL BACKGROUND
In this lawsuit, Endo alleges that Actavis has infringed the 737 patent and U.S. Patent
8,871,779 (which is not at issue on this motion) by (i) selling an FDA-approved extended-release
formulation of oxymorphone, and (ii) submitting an Abbreviated New Drug Application
(ANDA) seeking FDA approval for a different formulation of the same drug. Actavis moved
to dismiss Endos claims for direct, contributory, and induced infringement of the 737 patent,
showing that (1) all claims of the 737 patent are directed to an unpatentable law of nature under
35 U.S.C. 101, and (2) the Complaint failed to state a claim for indirect infringement and
cannot state a claim against Actavis for direct infringement. The R&R found that the 737
1
patents claims were unpatentable, and did not reach the issue of whether Endo had adequately
pled indirect infringement.
Claim 1 of the 737 patent is representative of all of the 737 patents claims:
1. A method of treating pain in a renally impaired patient, comprising the steps of:
a. providing a solid oral controlled release dosage form, comprising:
i. about 5 mg to about 8 mg of oxymorphone or a pharmaceutically acceptable
salt thereof as the sole active ingredient; and
ii. a controlled release matrix;
b. measuring a creatinine clearance rate of the patient and determining it to be (a)
less then about 30 ml/min, (b) about 30 mL/min to about 50 mL/min, (c) about 51
mL/min to about 80 mL/min, or (d) above about 80 mL/min; and
c. orally administering to said patient, in dependence on which creatinine clearance
rate is found, a lower dosage of the dosage form to provide pain relief;
wherein after said administration to said patient, the average AUC of oxymorphone
over a 12-hour period is less than about 21 nghr/mL.
The dependent claims modify either the value or the specified measurement of the final
wherein clause, and do not affect the present analyses.
ARGUMENT
I.
The R&R correctly concluded that the 737 patents claims were invalid as claiming
an unpatentable law of nature
Alice and Mayo set forth a two-part test of patent eligibility. First, a court must
determine if a relevant claim is directed to one of those patent ineligible concepts, i.e., a law of
nature, natural phenomenon, or an abstract idea. If so, then the court must ask, what else is
there in the claims before us? D.I. 51 at 9-10 (citing Alice, 134 S. Ct. at 2355).
A.
The 737 patents claims are directed to the law of nature that
bioavailability of oxymorphone is increased in patients with
renal impairment
The R&R recognized that Endo conceded in its original opposition brief that the relevant
claims are directed to a law of nature; Endo wrote that it is true that the claimed inventions
relate to the unexpected discovery that the bioavailability of oxymorphone is increased in
patients with renal impairment. D.I. 51 at 13 n. 70 (quoting D.I. 18 at 14). Endos argument
that the invention is directed instead to a new and useful regimen for treating pain in a specific
patient population is flatly contradicted by the 737 patent specification, which states that
oxymorphone and other morphine derivatives have been used for treating pain for decades (737
patent at 1:9-32), and that controlled release oxymorphone was approved by the FDA in 2006,
four years before the filing date of the 737 patent (737 patent at 3:40-49). The specification
describes the invention in simplest form as nothing more than providing prior art controlledrelease oxymorphones tablet and informing the patient or the patients prescribing physician
that the bioavailability of oxymorphone is increased in patients with renal impairment. 737
patent at 2:29-34. There is no question that the claims are directed to the law of nature that the
bioavailability of oxymorphone is increased in patients with renal impairment.
That Endo drafted its claims to require administration of a dosage of a drug (D.I. 56 at 34) does not show that the claims are to a new and useful process rather than a law of nature, as
Endo suggests. The claims step of administering the drug is insignificant post-solution
activity. Mayo, 132 S. Ct. at 1298 (quoting Diamond v. Diehr, 450 U.S. 175, 191-92 (1980)).
Mayo held unpatentable claims that included the step of determin[ing] the level of the relevant
metabolites in the blood, through whatever process the doctor or the laboratory wishes to use,
because scientists routinely measured metabolites as part of their investigations into the
relationships between metabolite levels and efficacy and toxicity of thiopurine compounds. Id.
3
Here, the administering step Endo relies on to argue for patent-eligibility calls for an even
more routine activity: giving an old drug (oxymorphone) for its known purpose (reducing pain).
There is nothing new and useful, to use Endos words (D.I. 56 at 3), about using the smallest
effective dose of a drug, or giving less to patients who need (or can only tolerate) less.
B.
The R&R correctly concluded that nothing in the 737 patents

claims transforms them into patent-eligible subject matter
The 737 patent claims: (1) providing a controlled release dosage of oxymorphone; (2)
measuring a creatinine clearance rate, which is used to measure renal impairment; and (3)
administering to the patient a lower dose of oxymorphone dependent on the creatinine clearance
rate measured. Neither Endos opposition brief nor its objections to the R&R argue that the
providing step or the measuring step provide patent-eligible subject matter. D.I. 18 at 14-20;
D.I. 56 at 3-9. Nor do they. Mayo, 132 S. Ct. at 1297-98 (steps directed to routine and
conventional medical activities do not provide patentable subject matter to laws of nature).
The R&R correctly found that the 737 patents administering step is analogous to the
indicates a need steps in Mayo. The measuring and administering steps of the 737 patent
are strikingly similar to the determining and wherein steps held unpatentable in Mayo, as
shown by the following table:
Claim 1 of the Mayo patent
132 S. Ct. at 1295
Claim 1 of the 737 patent
(b) determining the level of 6-thioguanine in

said subject having said immune-mediated
gastrointestinal disorder,
b. measuring a creatinine clearance rate of the

patient and
wherein the level of 6-thioguaninine less than

determining it to be (a) less than about 30

mL/min, (b) about 30 mL/min to about 50
mL/min, (c) about 51 mL/in to about 80
indicates a need to increase the amount of said
c. orally administering to said patient, in
dependence on which creatinine clearance rate

is found, a lower dosage of the dosage form to
provide pain relief
drug subsequently administered to said subject

and
wherein the level of 6-thioguanine greater than

wherein after said administration to said
indicates a need to decrease the amount of drug patient, the average AUC of oxymorphone
over a 12-hour period is less than about 21
subsequently administered to said subject.
nghr/mL.
Both the Mayo claim and the 737 patent claim providing or administering an old drug for a
known purpose, running lab work, and setting the dose of drug based on the results. The only
distinction is that the lab work in Mayo indicates a need to increase or decrease the drug, while
the 737 patent says to actually do it. But this is a distinction without a difference: there is no
meaningful addition to the law of nature in either claim. Contrary to Endos argument that
requiring a physician to apply that knowledge in [a] practical, tangible way (D.I. 56 at 5)
renders a claim patentable, the Supreme Court clearly held that one must do more than simply
state the law of nature while adding the words apply it. Mayo, 132 S. Ct. at 1294.
The Magistrate Judge also correctly distinguished the Classen series of cases. First,
Endos reliance on Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir.
2011) (Classen I), is misplaced because it is no longer good law after Mayo and Alice. It does
not matter that the Federal Circuit suggested in 2011 that stating the abstract idea of comparing
data on vaccination schedules and telling a doctor to apply it by administering vaccines
according to the preferred schedule rendered a claim patentable, when the Supreme Court held in
2012 in Mayo that merely adding an application step does not render a claim patentable. Indeed,
Classen I expressly relied on principles that Mayo rejected, i.e., the proposition that adding a
physical act to an unpatentable scientific principle renders the claim patent-eligible. See Classen
I, 659 F.3d at 1067-68 (In contrast, the claims of the 139 and 739 patents require the further
act of immunization in accordance with a lower-risk schedule, thus moving from abstract
scientific principle to specific application.). And if this was not enough, the Supreme Courts
admonition in Mayo, 132 S. Ct. at 1299-1300, and Alice, 134 S. Ct. at 2358-59, against finding
claims to be patentable solely due to the inclusion of an application step, thus overturned Classen
Is suggestion that adding an application step rendered a claim patentable.
Second, the subsequent decision of the District of Maryland on remand in Classen
Immunotherapies, Inc. v. Biogen IDEC, Civ. No. WDQ-04-2607, 2012 WL 326491 at *4-*5 (D.
Md. Aug. 9, 2012) (Classen II), apart from not being binding precedent on this Court,
distinguished Mayo on the ground that the application step in Mayo was well-understood,
routine, conventional activity previously engaged in by scientists who work in the field,
whereas there was no evidence that the immunization schedules at issue in Classen II were
conventional activity. As the R&R correctly noted, the 737 patent recognizes that the
administration of oxymorphone for pain relief is well-understood, routine, conventional activity,
making it equivalent to the patent-ineligible claim of Mayo, not the claim held to be patenteligible in Classen II. D.I. 51 at 16. Notably, the 737 patent claim does not require
administration of oxymorphone on any particular schedule or in any particular unusual way; it
merely requires the step of administering to said patient, in dependence on which creatinine
clearance rate is found, a lower dosage of the dosage form to provide pain relief. Mayo
similarly warned that its determining step was set forth in highly general language covering
all processes that make use of the correlations after measuring metabolites, including later
discovered processes that measure metabolite levels in new ways. 132 S. Ct. at 1302.
C.
The R&R correctly found that the 737 patent claims would
preempt future inventions and discoveries in the field
Endo claims that the 737 patent is limited to a specific method of treating a very
particular patient population (renally impaired patients) using a very particular drug (controlled
release oxymorphone) in a very particular way (reducing the dosage in dependent [sic] upon the
patients creatinine clearance rate). D.I. 56 at 9. So, too the Mayo patent was limited to a
specific method of treating a very particular patient population (patients with immune-mediated
gastrointestinal disorder) using a very particular drug (6-thioguanine) in a very particular way
(increasing or reducing the dosage dependent on whether the patients 6-thioguanine level was
below or above the range of 230-400 pmol per 8x108 red blood cells). 132 S. Ct. at 1295. The
Supreme Court explicitly rejected the exact same argument Endo makes here:
In any event, our cases have not distinguished among different
laws of nature according to whether the principles they embody are
sufficiently narrow. And this is understandable. Courts and judges
are not institutionally well suited to making the kinds of judgments
needed to distinguish among different laws of nature. And so the
cases have endorsed a bright-line prohibition against patenting
laws of nature, mathematical formulas and the like, which serves
as a somewhat more easily administered proxy for the underlying
building-block concern.
132 S. Ct. at 1303 (citations omitted).
The 737 patent, if it were held patentable, would dangerously preempt good
pharmaceutical and good medical practice. In the 737 patent, Endo did nothing more than
observe how a drug was metabolized in patients with kidney disease, and attempt to claim a
monopoly on good medical practice (adjusting the dosage of medicine in patients who need or
can tolerate less). The 737 patent seeks to prevent doctors from applying the good medical
practice of adjusting the dosage of an opiate painkiller to reduce side effects while maintaining
efficacy, and to prevent generic pharmaceutical companies from providing doctors with basic
medical information that can be helpful to their prescribing practices. These are among the
policy concerns that the patentable subject matter doctrine, and its focus on preemption, are
designed to address. See Mayo, 132 S. Ct. at 1302.
The Court in Mayo recognized the problem, raised by amici including the American
Medical Association and the American Hospital Association, that if claims to exclusive rights
over the bodys natural responses to illness and medical treatment are permitted to stand, the
result will be a vast thicket of exclusive rights over the use of critical scientific data that must
remain widely available if physicians are to provide sound medical care. 132 S. Ct. at 1304.
Putting medical information on the label of a drug, getting a patent, and then suing others for
infringement because they include that information on their labels is at the core of such concerns.
D.
The R&Rs reasoning would not lead to invalidation of all

method-of-treatment patents
As explained in this brief and the R&R, the 737 patents claims are not patent-eligible
subject matterand can be found to be patent-ineligible on a motion to dismissbecause the
patent itself states that all of the claim elements other than the law of nature are routine and
conventional activity. Endos sky is falling argument is largely nonsense. An inventor can
still discover that a known drug has some hitherto-unknown uses (as for different indications)
and claim a method of using that drug for the new use. The R&R stands only for the
unremarkable proposition that one cannot observe the way the body metabolizes an old drug
used for an old purpose, and seek to patent the use of that knowledge.
II.
If the Court finds that the R&R is in error, the Court should remand Actaviss
motion to dismiss to the Magistrate Judge for further consideration of the alternate
ground of no induced infringement
Actaviss motion to dismiss raised two grounds for dismissal: (1) invalidity of the 737
patent for claiming unpatentable subject matter, and (2) failure to state a claim of induced
infringement against Actavis. The Magistrate Judge, having found the patent invalid, did not
need to reach the issue of inducement. D.I. 51 at 18. Accordingly, if the Court does not adopt
the R&R, the motion to dismiss will not have been resolved completely, and the issue of whether
Endo sufficiently pled infringement of the 737 patent should be returned to the Magistrate Judge
(or decided in the first instance by the Court as it sees fit).
CONCLUSION
For the foregoing reasons, Actavis respectfully urges the Court to adopt the Magistrate
Judges Report and Recommendations and dismiss Counts I, III, and IV of the Complaint.

TAYLOR, LLP
Of Counsel:
Charles A. Weiss
31 West 52nd Street
New York, NY 10019
(212) 513-3551
/s/ Robert M. Vrana

Rodney Square
(302) 571-6600
apoff@ycst.com
rvrana@ycst.com

01:17916345.1
I, Robert M. Vrana, hereby certify that on October 30, 2015, I caused to be electronically
P.O. Box 1347
I further certify that on October 30, 2015, I caused a copy of the foregoing document
Dechert LLP
Suite 700
Sharon K. Gagliardi, Esquire
Julie M. Latsko, Esquire
Joseph J. Gribbin, Esquire
Dechert LLP
Circa Centre
2929 Arch Street
sharon.gagliardi@dechert.com
julie.latsko@dechert.com
joseph.gribbin@dechert.com
01:16529567.1

Brian Goldberg, Esquire
Dechert LLP
902 Carnegie Center, Suite 500
Princeton, NJ 08540
brian.goldberg@dechert.com
Blake B. Greene, Esquire
Dechert LLP
300 W. 6th Street, Suite 2010
Austin, TX 78701
blake.greene@dechert.com
Attorneys for Plaintiff Endo Pharmaceuticals Inc.
Jeffrey J. Toney, Esquire
Marcus A. Barber, Esquire
333 Twin Dolphin Drive, Suite 200
Redwood Shores, CA 94065
jtoney@kasowitz.com
mbarber@kasowitz.com
Rodney R. Miller, Esquire
Paul G. Williams, Esquire
1349 W. Peachtree Street, N.W., Suite 1500
Atlanta, GA 30309
rmiller@kasowitz.com
pwilliams@kasowitz.com
Attorneys for Plaintiff Mallinckrodt LLC
TAYLOR, LLP
/s/ Robert M. Vrana

Rodney Square
1000 N. King Street
rvrana@ycst.com
2
01:16529567.1

Briefs in Support of Motion To Dismiss For Invalidity Unpatentable Subject Matter Under 35 U.S.C Section 101 Briefs in Endo V Actavis Kidney Function Patent Delaware Case

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Briefs in Support of Motion To Dismiss For Invalidity Unpatentable Subject Matter Under 35 U.S.C Section 101 Briefs in Endo V Actavis Kidney Function Patent Delaware Case

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Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 1 of 18 PageID #: 123

IN THE UNITED STATES DISTRICT COURT

C.A. No. 14-1381-RGA

OPENING BRIEF IN SUPPORT OF

YOUNG CONWAY STARGATT & TAYLOR LLP

Dated: January 20, 2015

Attorneys for Defendants Actavis Inc. and

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 2 of 18 PageID #: 124

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 3 of 18 PageID #: 125

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 4 of 18 PageID #: 126

Ricoh Co. v. Quanta Computer Inc.,

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 5 of 18 PageID #: 127

Defendants follow the Complaints lead of referring to both defendants collectively as

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 6 of 18 PageID #: 128

NATURE AND STAGE OF THE PROCEEDINGS

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 7 of 18 PageID #: 129

SUMMARY OF THE ARGUMENT

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 8 of 18 PageID #: 130

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 9 of 18 PageID #: 131

8.7 Renal Impairment

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 10 of 18 PageID #: 132

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 11 of 18 PageID #: 133

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 12 of 18 PageID #: 134

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 13 of 18 PageID #: 135

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 14 of 18 PageID #: 136

Claim 1 of the 737 patent

1. A method of optimizing therapeutic efficacy

1. A method of treating pain in a renally

a. providing a solid oral controlled release

(b) determining the level of 6-thioguanine in

b. measuring a creatinine clearance rate of the

wherein the level of 6-thioguaninine less than

wherein after said administration to said

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 15 of 18 PageID #: 137

wherein the level of 6-thioguaninine greater

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 16 of 18 PageID #: 138

/s/ Adam W. Poff

Dated: January 20, 2015

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 17 of 18 PageID #: 139

Case 1:14-cv-01381-RGA Document 12 Filed 01/20/15 Page 18 of 18 PageID #: 140

Dated: January 20, 2015

YOUNG CONAWAY STARGATT &

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 1 of 15 PageID #: 330

IN THE UNITED STATES DISTRICT COURT

C.A. No. 14-1381-RGA

REPLY BRIEF IN FURTHER SUPPORT OF

YOUNG CONWAY STARGATT & TAYLOR LLP

Dated: March 23, 2015

Attorneys for Defendants Actavis Inc. and

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 2 of 15 PageID #: 331

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 3 of 15 PageID #: 332

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 4 of 15 PageID #: 333

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 5 of 15 PageID #: 334

ENDO CANNOT SUSTAIN A CLAIM FOR INFRINGEMENT ON THE

providing a solid oral controlled release dosage of oxymorphone

measuring a creatinine clearance rate of a patient;

determining that rate to be within one of four ranges (which

administering a lower dosage of oxymorphone in dependence on

after administration, either the average area-under-curve or

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 6 of 15 PageID #: 335

Case 1:14-cv-01381-RGA Document 20 Filed 03/23/15 Page 7 of 15 PageID #: 336

allegations to show inducement for the already-approved extended-release oxymorphone tablets.

Mere notice of Endos claims is insufficient to survive this motion to dismiss