Alvogen Response Brief

Case: 18-2361 Document: 31 Page: 1 Filed: 01/09/2019
2018-2361
PERNIX IRELAND PAIN DAC, PERNIX THERAPEUTICS, LLC,

Plaintiffs Appellants,
v.
ALVOGEN MALTA OPERATIONS LTD.,
Defendant Appellee.
Appeal from the United States District Court

for the District of Delaware in Case No. 1:16-Cv-00139-WCB,
Judge William C. Bryson Sitting by Designation
BRIEF FOR APPELLEE

ALVOGEN MALTA OPERATIONS LTD.
Matthew J. Becker Christopher M. Gallo

Chad A. Landmon AXINN, VELTROP & HARKRIDER LLP
Edward M. Mathias 950 F St NW
Thomas K. Hedemann Washington, DC 20004
David K. Ludwig (202) 721-5413
AXINN, VELTROP & HARKRIDER LLP cgallo@axinn.com
90 State House Square
Hartford, Connecticut 6103
(860) 275-8100
mbecker@axinn.com
clandmon@axinn.com
tmathias@axinn.com
thedemann@axinn.com
dludwig@axinn.com
Attorneys for Appellee Alvogen Malta Operations Ltd.
January 9, 2019
COUNSEL PRESS, LLC (202) 783-7288
CERTIFICATE OF INTEREST
Pursuant to Federal Circuit Rule 47.4, Counsel for Appellee Alvogen Malta
Operations Ltd. certifies the following:
1. The full name of every party or amicus represented by me is:
Alvogen Malta Operations Ltd.
2. The name of the real party in interest represented by me is:
3. All parent corporations and any publicly held companies that own 10 percent or
more of the stock of the party or amicus curiae represented by me are:
Alvogen Lux Holdings S.a.r.l; Alvogen Pharma Ltd.
4. The names of all law firms and the partners or associates that appeared for the
party or amicus now represented by me in the trial court or agency or are expected
to appear in this court (and who have not or will not enter an appearance in this
case) are:
Axinn, Veltrop & Harkrider LLP: Ryan D. Hersh, Seth I. Heller

Shaw Keller LLP: Karen E. Keller, David M. Fry, Jeff Castellano, Nathan R.
Hoeschen
5. The title and number of any case known to counsel to be pending in this or any
decision in the pending appeal.
None
Dated: January 9, 2019 /s/ Chad A. Landmon

Chad A. Landmon
Attorney for Appellee
i
TABLE OF CONTENTS
STATEMENT OF RELATED CASES .....................................................................1

PRELIMINARY STATEMENT ...............................................................................1
STATEMENT OF THE ISSUES...............................................................................3
STATEMENT OF THE CASE ..................................................................................4

I. Technical Background and the Prior Art .........................................................4
A. Prior Art Hydrocodone Formulations ...................................................4

B. Opioid Metabolism in Patients with HI. ...............................................5
II. The Asserted Patents........................................................................................6
SUMMARY OF ARGUMENT .................................................................................8
I. The District Court Correctly Held

that the Asserted Claims Are Invalid as Obvious............................................8
II. The District Court Correctly Held that the
Asserted Claims are Invalid as Lacking Written Description. ......................10
ARGUMENT ...........................................................................................................11
I. The District Court Correctly Held
That the Asserted Claims Are Invalid as Obvious. .......................................11
to Combine and Reasonable Expectation of Success..........................13
1. ......14
2.
the IR Combination Products Are Correct................................22
......25
1.
Relating to Obviousness Are Internally Consistent. .................26
ii
2. Pernix Misrepresents the Standard for Reasonable

............28
3.
Description and Obviousness Are Fully Consistent. ................30
The District Court Correctly Applied

Inherency Principles in Its Obviousness Analysis. .............................32
The District Court Properly Considered the Objective Indicia. ..........34
1. The District Court Did Not Reach Its Conclusion on
Obviousness Prior to Considering the Alleged Indicia.............34
2. The District Court Properly Assessed
lure of Others...................................35
3. The District Court Correctly
Found No Unexpected Results..................................................37
E. The District Court Did Not Misinterpret the Asserted Claims. ..........39
II. The District Court Correctly Held That the

Asserted Claims Are Invalid as Lacking Written Description. .....................41
A.
.................................43
B. The District Court Correctly

Found that the Specifications Do Not
Demonstrate Possession of the Claimed Genus. .................................46
The Specifications Do Not
Disclose a Representative Number of Species. ........................47
The Specifications Do Not Disclose

Structural Features Common to the Claimed Genus. ...............51
C. ....................54
1. Feutterer and Herschler Are Distinguishable
Because They Are Directed to Different Types of Claims. ......55
iii
2. Alcon Concerns Different Types of Claims

and Different Issues. .................................................................57
3. Union Oil Is Inapposite. ............................................................60

D. ................................60
CONCLUSION ........................................................................................................61
iv
TABLE OF AUTHORITIES
Page
Cases
AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc.,
759 F.3d 1285 (Fed. Cir. 2014) ................................ 42, 45, 46, 47, 48, 49, 50, 59
Alcon Research Ltd. v. Barr Labs., Inc.,

745 F.3d 1180 (Fed. Cir. 2014) ............................................. iv, 57, 58, 59, 60, 61
Allergan, Inc. v. Sandoz Inc.,
726 F.3d 1286 (Fed. Cir. 2013) ...........................................................................29
Amgen Inc. v. Hoechst Marion Roussel, Inc.,
314 F.3d 1313 (Fed. Cir. 2003) .................................................................... 31, 46
Apple Inc. v. Motorola, Inc.,
757 F.3d 1286 (Fed. Cir. 2014) ...........................................................................25
Ariad Pharms., Inc. v. Eli Lilly & Co.,
598 F.3d 1336 (Fed. Cir. 2010) (en banc) ...................... 10, 41, 44, 45, 47, 51, 53
Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,

752 F.3d 967 (Fed. Cir. 2014)..............................................................................38
Chapman v. Casner,
......................................................................40
Cooper Cameron Corp. v. Kvaerner Oilfield Prods., Inc.,

291 F.3d 1317 (Fed. Cir. 2002) .................................................................... 56, 57
DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
567 F.3d 1314 (Fed. Cir. 2009) ...........................................................................29
Endo Pharm. Inc. v. Teva Pharm. USA, Inc.,

............................................................... 33, 34
Funk v. Stryker Corp.,

631 F.3d 777 (5th Cir. 2011) ...............................................................................16
Gentry Gallery, Inc. v. Berkline Corp.,

134 F.3d 1473 (Fed. Cir. 1998) ...........................................................................57
v
,
....................................................................30
,
618 F.3d 1294 (Fed. Cir. 2010) ...........................................................................37
Hybritech Inc. v. Monoclonal Antibodies, Inc.,

802 F.2d 1367 (Fed. Cir. 1986) ...........................................................................37
In re Alonso,
545 F.3d 1015 (Fed. Cir. 2008) .................................................................... 47, 59
In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig.,
676 F.3d 1063 (Fed. Cir. 2012) ...........................................................................35
In re Droge,
695 F.3d 1334 (Fed. Cir. 2012) ...........................................................................29
In re Fuetterer,
319 F.2d 259 (C.C.P.A. 1963) ...................................................................... 55, 56
In re Herschler,
591 F.2d 693 (C.C.P.A. 1979) ........................................................... iv, 55, 56, 58
In re Oelrich,
666 F.2d 578 (C.C.P.A. 1981) .............................................................................33
In re Theresa,
.....................................................................40
In Re: Copaxone Consol. Cases,

906 F.3d 1013 (Fed. Cir. 2018) ...........................................................................18
Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino,

738 F.3d 1337 (Fed. Cir. 2013) ...........................................................................29
KSR Int'l Co. v. Teleflex Inc.,
550 U.S. 398 (2007) .............................................................................................29
Par Pharm., Inc. v. TWi Pharm., Inc.,
773 F.3d 1186 (Fed. Cir. 2014) ........................................ 9, 13, 17, 23, 32, 33, 34
vi
Perricone v. Medicis Pharm. Corp.,

432 F.3d 1368 (Fed. Cir. 2005) ...........................................................................33
Pfizer, Inc. v. Apotex, Inc.,

480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 17, 28
Polaroid Corp. v. Eastman Kodak Co.,

789 F.2d 1556 (Fed. Cir. 1986) ...........................................................................14
Ransomes, Inc. v. Great Dane Power Equip., Inc.,
232 F.3d 911 (Fed. Cir. 2000)..............................................................................37
Regents of the Univ. of Cal. v. Eli Lilly & Co.,
119 F.3d 1559 (Fed. Cir. 1997) ...........................................................................47
Sanofi v. Watson Labs., Inc.,

875 F.3d 636 (Fed. Cir. 2017)..............................................................................30
Senju Pharm. Co. v. Lupin Ltd.,

780 F.3d 1337 (Fed. Cir. 2015) .................................................................... 20, 53
Stratoflex, Inc. v. Aeroquip Corp.,

713 F.2d 1530 (Fed. Cir. 1983) ...........................................................................36
Tyco Healthcare Grp. LP v. Mut. Pharm. Co.,

642 F.3d 1370 (Fed. Cir. 2011) ...........................................................................39
Union Oil Co. of Cal. v. Atlantic Richfield Co.,

208 F.3d 989 (Fed. Cir. 2000)........................................................................ iv, 60
Univ. of Rochester v. G.D. Searle & Co.,

358 F.3d 916 (Fed. Cir. 2004)................................................................. 46, 49, 59
Vas-Cath Inc. v. Mahurkar,

935 F.2d 1555 (Fed. Cir. 1991) ...........................................................................57
Yeda Research v. Mylan Pharm. Inc.,
906 F.3d 1031 (Fed. Cir. 2018) ...........................................................................18
Rules
Fed. R. Evid. 201(b)(2) ............................................................................................16
Fed. R. Evid. 201(c)(1) ............................................................................................16

vii
Fed. R. Evid. 201(d) .................................................................................................16
viii
TABLE OF ABBREVIATIONS
Abbreviation Description
Pernix Pernix Ireland Pain DAC and Pernix Therapeutics, LLC
Alvogen Alvogen Malta Operations Ltd.
760 patent U.S. Patent No. 9,265,760
499 patent U.S. Patent No. 9,339,499
Asserted Patents 760 patent and 499 patent
Claims 1-4, 11, 12, 17 and 760 patent and claim 1

Asserted Claims
499 patent
HI Hepatic impairment
Hydrocodone-
Having hydrocodone bitartrate as the only active ingredient
only
IR Immediate release
ER Extended release
PK Pharmacokinetic(s)
POSA Person of ordinary skill in the art
PPA Patient-prescriber agreement
FDA Guidance for Industry: Pharmacokinetics in Patients

FDA Guidance with Impaired Hepatic Function: Study Design, Data
Analysis, and Impact on Dosing and Labeling (May 2003)
FDA Drug Safety Communication: Prescription

FDA
Acetaminophen Products to Be Limited to 325 mg Per
Acetaminophen
Dosage Unit; Boxed Warning Will Highlight Potential for
Communication
Severe Liver Failure (January 2011)
ix
Devane U.S. Patent Application Publication No. 2006/0240105 A1
Devane
Formulation disclosed in Devane identical to Zohydro ER
Formulation
Jain U.S. Patent Application Publication No. 2010/0010030 A1
Area under the curve of the plasma concentration of an active

AUC
pharmaceutical ingredient over time following a dosing event
Maximum concentration observed in the blood following

Cmax
delivery of an active pharmaceutical ingredient
One-Step Claims
499 patent
Two-Step Claims Claims 1-4 and 11 760 patent
760 patent claim 2) wherein the dosage unit provides a

release profile of hydrocodone that does not increase average
hydrocodone AUC0-inf in subjects suffering from mild hepatic
impairment relative to subjects not suffering from renal or
hepatic impairment in an amount of more than 30%, and the
release profile of hydrocodone does not increase average
hydrocodone AUC0-inf in subjects suffering from moderate
hepatic impairment relative to subjects not suffering from
renal or hepatic impairment in an amount of more than 50%

PK Limitations release profile of hydrocodone that does not increase average
hydrocodone AUC0-inf in subjects suffering from mild hepatic
hydrocodone AUC0-inf in subjects suffering from moderate

hydrocodone Cmax in subjects suffering from mild hepatic
x

hydrocodone Cmax in subjects suffering from moderate

hydrocodone AUC0-inf per 20 mg of hydrocodone bitartrate
dosed to subjects suffering from moderate hepatic
impairment is in the range of about 352 ng*h/mL to about
666 ng*h/mL

release profile of hydrocodone that:
(1) does not increase average hydrocodone AUC0-inf in
subjects suffering from mild hepatic impairment relative to
subjects not suffering from renal or hepatic impairment in an
amount of more than 14%;
(2) does not increase average hydrocodone AUC0-inf in
subjects suffering from moderate hepatic impairment relative
to subjects not suffering from renal or hepatic impairment in
an amount of more than 30%;
(3) does not increase average hydrocodone Cmax in subjects
suffering from mild hepatic impairment relative to subjects
not suffering from renal or hepatic impairment in an amount
of more than 9%; and
(4) does not increase average hydrocodone Cmax in subjects
suffering from moderate hepatic impairment relative to
subjects not suffering from renal or hepatic impairment in an
amount of more than 14%

release profile of hydrocodone such that:
(1) the average hydrocodone AUC0-inf per 20 mg of
hydrocodone bitartrate dosed to subjects not suffering from
xi
renal or hepatic impairment is in the range of about 300

ng*h/mL to about 500 ng*h/mL;
hydrocodone bitartrate dosed to subjects suffering from mild
hepatic impairment is in the range of about 300 ng*h/mL to
about 570 ng*h/mL;
hydrocodone bitartrate dosed to subjects suffering from
moderate hepatic impairment is in the range of about 300
ng*h/mL to about 700 ng*h/mL

release profile of hydrocodone that:
does not increase average AUC0-inf in subjects suffering from
mild hepatic impairment relative to subjects not suffering
from renal or hepatic impairment in an amount of more than
14%; and
does not increase average AUC0-inf in subjects suffering from
moderate hepatic impairment relative to subjects not
suffering from renal or hepatic impairment in an amount of
more than 30%
Non-Adjustment 760 patent claims 1-4 at 11) wherein the starting dose is not
Limitation adjusted relative to a patient without hepatic impairment
xii
STATEMENT OF RELATED CASES
Counsel is not aware of any cases pending in this or any other court or
the pending appeal.
PRELIMINARY STATEMENT
There was nothing inventive about the Asserted Claims. The named
inventors merely took the prior art Devane Formulation, which was disclosed as
being useful for treating pain, and claimed the pharmacokinetic results from a
routine HI study required by FDA for marketing approval. The study showed that
the hydrocodone-only pharmacokinetics are similar in subjects with
and without mild or moderate HI. These results dictated that no downward dose
adjustment for mild or moderate HI subjects was necessary because it was well
known that dose adjustments were only required where the pharmacokinetics in the
two subject populations were substantially different. The lack of any need for dose
adjustment with the Devane Formulation was not surprising: Jain had already
disclosed similar pharmacokinetics for an ER hydrocodone formulation in such
subjects, and none of the widely-used IR hydrocodone formulations required a
dose adjustment when used to treat pain in patients with mild or moderate HI.
Judge Bryson (sitting by designation) therefore correctly found that a POSA would
have been motivated to administer the Devane Formulation to patients with mild or
1
moderate HI, and would have reasonably expected to successfully treat their pain
without adjusting the starting dose.
Understanding that it cannot meet the high burden of demonstrating that the
well-supported factual findings are clearly erroneous, Pernix
instead incorrectly characterizes them , or asserts that they are
with other findings. This Court should reject
both tactics. First, it is black letter patent law that findings concerning motivation
to combine and reasonable expectation of success are factual findings reviewed for
clear error. Second, Pernix relies on sentence fragments from the District Court
opinion that, when viewed in their appropriate context, are revealed as sound
findings rather than Pernix has not and cannot identify any
reversible error in the District , which this Court
should affirm.
The Asserted Claims also lack adequate written description. The District
Court correctly found that the Asserted Claims recite a broad genus of ER
hydrocodone-only formulations that are functionally defined. Faithfully applying
the Asserted
Patents disclosed either a representative number of species falling within the scope
of the genus or structural features common to the members of the genus so that a
POSA could visualize or recognize the members of the genus. It made factual
2
findings that the Asserted Patents do not meet either criterion, instead disclosing
only a single operative embodiment and providing no information as to the
structural features required to achieve the claimed functional limitations. Pernix
has not and cannot identify a basis to distu
written description, and this Court should affirm.
STATEMENT OF THE ISSUES

1. Has Pernix demonstrated that the District Court committed clear error
in finding that a POSA would have been motivated to combine the prior art
disclosing every limitation in the Asserted Claims with a reasonable expectation of
success in doing so, that the objective indicia are neutral or entitled to only
minimal weight, and that the District Court therefore erred in holding that the
Asserted Claims are invalid as obvious?
2. Has Pernix demonstrated that the District Court committed clear error
in finding that the Asserted Claims are invalid as lacking written description,
where the Asserted Claims recite a genus in functional terms, but the specification
discloses only a single species that meets the functional limitations and does not
identify any structural or formulation characteristics that give rise to the claimed
functions?
3
STATEMENT OF THE CASE
I. TECHNICAL BACKGROUND AND THE PRIOR ART

A. Prior Art Hydrocodone Formulations
Like other opioids, hydrocodone formulations have long been used for the
treatment of pain. (Appx476 (181:8-19), Appx3054.) Hydrocodone was first
approved in the United States to treat pain in 1943. (Appx3054.) Vicodin and
Lortab, which combine hydrocodone and acetaminophen, and Vicoprofen, which
combines hydrocodone and ibuprofen, are widely-used prior art IR products for the
treatment of pain. (Appx476 (181:15-24), Appx490-491 (195:15-196:21),
Appx2673, Appx3121, Appx3230.)
ER hydrocodone formulations were also well known in the prior art.
Devane, published in 2006, discloses an ER hydrocodone-only formulation that
would eventually become known as Zohydro ER. (Appx479-480 (184:9-185:16),
Appx483 (188:1-15), Appx3604, Appx3617 (¶32), Appx3624 (¶¶99-101).) Jain,
published in 2010, discloses an ER hydrocodone/acetaminophen combination
formulation known as Vicodin CR. (Appx491 (196:12-21), Appx3631, Appx3647
(¶34).) Both Devane and Jain teach that the disclosed formulations are used for the
treatment of pain. (Appx3620 (¶70), Appx3647 (¶34).) A third ER hydrocodone
(plus chlorpheniramine) product, TussiCaps, was approved for cold symptoms as
of 2008. (Appx2687-2688, Appx2598.)
4
B. Opioid Metabolism in Patients with HI
It has long been understood that patients with HI especially more severe
HI might experience elevated blood levels when taking drugs that, like opioids,
are significantly metabolized by the liver because HI slows drug metabolism.
(Appx472 (177:9-23).) FDA has responded with labeling guidance recommending
dose reductions for HI patients when the effect of that HI on drug metabolism is
two-fold [+100%] or greater increase in AUC). (Appx474-476
(179:13-181:7), Appx3573.)
Consistent with FDA guidance, opioid drug labels often contain warnings
or instructions to reduce dosage when treating patients with HI, based on the
severity and the pharmacokinetic properties. The prior art labels for
Vicodin, Lortab, Vicoprofen and TussiCaps (all containing hydrocodone), for
example,
severe impairment of hepatic or renal function, but do not contain any warning or
dosing adjustment recommendation with respect to patients with mild or moderate
HI. (Appx2677, Appx2689, Appx3121, Appx3231.)
Jain discloses a pharmacokinetic study of Vicodin CR in patients with mild
or moderate HI. (Appx491 (196:22), Appx3649 (¶64).) It reports that the
pharmacokinetic parameters of hydrocodone in patients with mild or moderate HI
were in normal patients. (Appx492 (197:1-24), Appx3649
5
(¶64).) For a number of reasons, a POSA would
qualitative statement . . . means that a dose adjustment would not be not required
for patients with mild or moderate [HI]. (Appx493 (198:1-7); see also Appx781
(486:10-23).) For example, understood that a [HI] study is
conducted to determine whether a dose adjustment is required, and . . . a report of
Prior art labels for opioids other than hydrocodone have a variety of
warnings. Nucynta (tapentadol) recommends dose adjustment for patients with
moderate HI, but states that no dose adjustment is necessary for patients with mild
HI. (Appx544 (249:11-20), Appx2707.) The labels for Exalgo (hydromorphone),
Kadian (morphine) and Avinza (also morphine) similarly recommend dose
adjustment for patients with moderate or severe HI, but do not mention mild HI.
(Appx545-548 (250:16-253:3), Appx2772, Appx2663, Appx2757.) The
oxycodone drug, OxyContin, and the oxymorphone drugs, Opana and Opana ER,
exhibit the most pronounced HI effect, and their labels accordingly recommend
dose adjustment for all HI patients regardless of severity. (Appx5005, Appx3910.)
II. THE ASSERTED PATENTS
The Asserted Patents are based entirely on a routine HI study of the Devane
Formulation. (Appx5044-5045, Appx575 (280:15-19), Appx654 (359:10-19).)
6
When Zogenix, the original NDA owner, sought FDA approval to market the
Devane Formulation, FDA required the company to conduct an HI study to
determine whether the drug label should include prescribing instructions or
restrictions for patients with HI. (Id., Appx6.) Consistent with results, of
which the named inventors professed to have no awareness, the study data showed
that the pharmacokinetics were similar for normal patients
and patients with mild or moderate HI. (Appx6.)
Zogenix filed a patent application shortly thereafter, reproducing the
formulation information published in Devane and reporting the pharmacokinetic
data from the HI study as an allegedly unexpected result. (Appx667-668 (372:24-
373:9) (study performed in 2011), Appx2782 (first provisional application filed in
2012).) Although the named inventors also included (again, directly from Devane)
additional IR formulations and ER coating solutions that can be used in various
permutations to create numerous ER hydrocodone-only formulations (Appx2801
(21:32-65 (Tables 1 and 2))), they did not test any other hydrocodone formulations.
The Asserted Patents have two sets of claims, which the District Court
- - (Appx10.) The
One-Step Claims simply require the treatment of a patient with mild or moderate
HI by administering a ER hydrocodone-only dosage form that exhibits a series of
pharmacokinetic parameters. (Id.) These parameters relate to the relationship
7
Cmax in normal patients as compared to patients with
mild or moderate HI, and reflect the results of the HI study (using the Devane
Formulation) described in the Asserted Patents. (Id.) The Two-Step Claims add
that a physician of the dosage form that is not
adjusted relative to the dose that would have been prescribed to a patient without
mild or moderate HI. (Id.)
Although the pharmacokinetic data reported in the Asserted Patents relates
exclusively to the Devane Formulation, the Asserted Claims are not limited to that
formulation. Rather, the only limitations in the Asserted Claims pertaining to
formulation are that the oral -
extended release (Appx2802-2803, Appx3052-3053), thus encompassing an
essentially limitless number of formulation species (Appx90).
SUMMARY OF THE ARGUMENT
I. THE DISTRICT COURT CORRECTLY HELD THAT

THE ASSERTED CLAIMS ARE INVALID AS OBVIOUS.
The District Court obviousness conclusion follows straight-forwardly from
the trial evidence. The inventors copied the ER hydrocodone-only formulation
from Devane and claimed its inherent pharmacokinetic properties. Furthermore,
Jain disclosed that an ER hydrocodone formulation provided similar
pharmacokinetics in patients with and without mild or moderate HI and thus did
not require dose adjustment. Dose adjustment was also not required for the prior
8
art IR hydrocodone formulations, which had for decades been used to treat pain in
patients with HI. demonstrate that the
Court should reverse the District Court s conclusion.
First, Pernix cannot demonstrate well-supported
factual findings
expectation of success are clearly erroneous. And t
attempt to sidestep the deferential clear-error standard by mislabeling these
findings See Par Pharm., Inc. v. TWi Pharm., Inc., 773 F.3d
1186, 1196 (Fed. Cir. 2014) (motivation to combine and reasonable expectation of
success are questions of fact).
Second, there is no basis for Pernix assertion that
factual findings are internally .
conflicts lack even facial credibility and result from reliance on sentence
fragments without providing factual and legal contexts.
Third, the District Court correctly held that the PK Limitations are inherent
in Devane. There is no dispute that it was obvious to administer the Devane
Formulation to patients with mild or moderate HI, nor any dispute that the PK
Limitations are necessarily present when so administered. They are therefore the
natural result of the operation as taught in the prior art and, consequently,
inherently disclosed.
9
Finally,
assertion that the District Court
reached its obviousness conclusion before considering the indicia is disproved by
the opinion itself. And the District Court correctly considered the alleged failure
of Vantrela in the context of the success of Vicodin CR and/or Hysingla ER, both
of which are ER hydrocodone formulations that do not require dose adjustment in
patients with mild or moderate HI. Lastly, the District Court correctly rejected
e Formulation did not
require dose adjustment. Pernix failed to consider Jain, the closest prior art, and
relied on self-serving testimony by inventors who were also unaware of Jain.
II. THE DISTRICT COURT CORRECTLY

HELD THAT THE ASSERTED CLAIMS ARE
INVALID AS LACKING WRITTEN DESCRIPTION.
The Asserted Claims are based on the PK results of an HI study performed
with only the prior art Devane Formulation. But they are broadly cast to cover use
of all hydrocodone-only ER dosage forms that meet the claimed PK values or do
not require dose adjustment. The District Court properly recognized this overreach
and concluded that the Asserted Claims lacked adequate written description. See
Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en
banc).
10
Pernix attempts to avoid the District
Court factual findings central to its written description decision by miscasting the
Asserted Claims as being limited to the administration of the Devane Formulation
the only dosage form in the Asserted Patents demonstrated to meet the PK and
Non-Adjustment Limitations. Pernix then seeks to parlay this misreading of the
claims to assert that the District Court applied the wrong legal standard in finding
the Asserted Claims invalid for lacking written description.
But the District Court explained in great detail why Pernix is wrong. It
found that the Asserted Claims are generic in nature and recite a method of
administering a genus of hydrocodone-only ER dosage forms that meet the claimed
PK values or do not require a dose adjustment in patients with mild or moderate
HI. It further found that the Asserted Patents do not disclose any embodiments
other than the prior art Devane Formulation that have been demonstrated to meet
the claimed functional limitations, or any structural features that would assist a
POSA in identifying species that fall within the claimed genus.
to argue otherwise have no merit, and the cases on which it relies are inapposite.
ARGUMENT
I. THE DISTRICT COURT CORRECTLY HELD THAT

THE ASSERTED CLAIMS ARE INVALID AS OBVIOUS.
Alvogen established the following key evidence at trial regarding the
obviousness of the Asserted Claims:
11
The named inventors copied the ER hydrocodone-only formulation

employed in the Asserted Patents from Devane, which also discloses
using the formulation to treat pain. (Appx5044-5045, Appx6,
Appx480-481 (185:20-186:3), Appx663-664 (368:6-369:3).)
The claimed PK Limitations are inherent to the Devane Formulation.

(Appx37, Appx65-69, Appx536-537 (241:21-242:8).)
Every hydrocodone formulation in the prior art, as well as every other

opioid, was administered to patients with mild or moderate HI. (Appx64,
Appx70-71.)
Jain discloses that Vicodin CR, an ER hydrocodone-acetaminophen

formulation, provides similar pharmacokinetics in patients with and without
mild or moderate HI (Appx79, Appx3649 (¶64)), and the labels for the
decades-old and widely-used IR hydrocodone-acetaminophen formulations
Vicodin and Lortab also did not require dose adjustment in patients with
mild or moderate HI. (Appx60, Appx497 (202:9-21), Appx498-499
(203:24-204:5).)
Based on this evidence, the District Court made the factual findings that a
POSA would have been motivated to combine Devane with Jain and the Vicodin
and Lortab labels, and would have had a reasonable expectation that the Devane
Formulation could successfully be administered to patients with mild or moderate
HI without dose adjustment. (Appx74.) In view of Jain and/or Vicodin and
Lortab, the District Court further
unexpected that the Devane Formulation did not require dose adjustment.
(Appx84-87.) And, finally, the District Court found that the alleged failure of
Vantrela had little significance in view of the success of and
Hysingla ER, both of which are ER hydrocodone formulations that do not require
12
dose adjustment. (Appx87-88.) Upon these straightforward factual findings, the
District Court concluded that the Asserted Claims would have been obvious in
view of Devane and Jain and/or the Vicodin and Lortab labels.
As set forth below, this conclusion
of obviousness because the District Court: (A) made factual findings that are well-
supported and consistent, and certainly not clearly erroneous; (B) correctly applied
inherency in the context of obviousness; and (C) appropriately considered the
asserted secondary indicia.
the Distric
Combine and Reasonable Expectation of Success.
Pernix incorrectly
findings about motivation to combine and reasonable expectation of success.
(Pernix.Br. at 24-37.
motivation to combine references in an obviousness determination is a pure
question of fact. The presence or absence of a reasonable expectation of success is
Par Pharm., 773 F.3d at 1196 (citation and internal
merely disagreements with the
District Co
clear error. Id. at 1194.
Id. (quoting Polaroid Corp. v.
13
Eastman Kodak Co., 789 F.2d 1556, 1559 (Fed. Cir. 1986)). Pernix does not come
close to demonstrating any clear error in the District Court
1. Findings Regarding Jain are Correct.

a. A POSA Would Have Been
Motivated to Combine Devane and Jain.
Jain discloses Vicodin CR, an ER hydrocodone-acetaminophen dosage form
suitable to treat pain in subjects with mild or moderate HI. (Appx3649 (¶64),
Appx491-493 (196:12-198:7).) The Devane Formulation also contains ER
hydrocodone but does not contain any additional active ingredients. (Appx483
(188:1-15), Appx3617 (¶32), Appx3624 (¶¶99-101).) Pernix argued that a POSA
would not have looked to Jain for guidance as to the correct dosing of the Devane
Formulation in HI patients because Devane does not contain acetaminophen.
(Appx71 (citing Pernix post-trial brief).) The District Court
argument for four distinct reasons:
1. Acetaminophen, unlike hydrocodone, is hepatotoxic. A hydrocodone-

only formulation would thus be comparatively safer for HI patients than a
combination hydrocodone-acetaminophen formulation. (Appx71.)
2.
hydrocodone-ibuprofen drug to approve Zohydro ER, i.e., the Devane
Formulation, demonstrates the relevance of the performance of
combination drugs to hydrocodone-only drugs. (Appx71-72.)
3. A POSA would have been motivated to formulate analgesics with little or

no acetaminophen in view of
use of acetaminophen in combination analgesics. (Appx72.)
14
4. [POSA] would have appreciated that

acetaminophen and hydrocodone are metabolized differently, and that
acetaminophen would not have had a significant impact on the
-73.)
erroneous because, Pernix contends, it is not supported by the FDA
Acetamino
hydrocodone and acetaminophen. (Pernix.Br. at 29-30 (citing Appx72).) Pernix is
wrong.
As an initial matter, the District Court supported its finding of a motivation
to combine with three other
would have known that acetaminophen does not affect the pharmacokinetics of
hydrocodone. (Appx72- one of four supporting
findings was incorrect is thus incapable o
larger finding was clearly erroneous.
Communication would further support a motivation to combine is well-supported
and certainly not clearly erroneous. The FDA Acetaminophen Communication
United States.
liver injury associated with the use of ace
15
additional regulatory actions such as . . . withdrawing prescription combination
products from the market, or reducing the amount of acetaminophen in each
the District Court found. (Appx72.)
Offering no legal support, Pernix
for the District Court to sua sponte take judicial notice of the FDA Acetaminophen
Communication. (Pernix.Br. at 29.) Pernix does not dispute, however, that the
y be
judicial notice of such facts. Fed. R. Evid. 201(b)(2). Nor does Pernix dispute that
Fed. R. Evid. 201(c)(1), (d). The District Court was thus well within its authority
to take judicial notice of the FDA Acetaminophen Communication. See, e.g., Funk
v. Stryker Corp., 631 F.3d 777, 783 (5th Cir. 2011) (appropriate for district court to
Finally, that Jain itself is not concerned with providing a single ingredient
formulation is irrelevant. (Pernix.Br. at 30.) The Devane Formulation is identical
to the ER hydrocodone-only formulation employed in the Asserted Patents and
16
thus did not require any modification to practice the Asserted Claims. (Supra at
12.) The relevant issue is thus whether a POSA would be motivated to administer
the Devane Formulation unadjusted to a patient with mild or moderate HI, not
whether a POSA would be motivated to remove the acetaminophen from Jain.1
b. Jain Provided a POSA with a

Reasonable Expectation of Success.
Pernix.Br. at 32.) First, a reasonable expectation of success does
not require absolute predictability. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1364 (Fed. Cir. 2007)
ngs with respect to the reasonable
expectation are issues of fact, not law. Par Pharm., 773 F.3d at 1196. They are
therefore entitled to deference and reviewed for clear error. Id.
Pernix does not come close to demonstrating any clear error. It points to the
absence of numerical pharmacokinetic data from the HI study described in Jain,
but cites no legal precedent holding that a reasonable expectation of success must
be based on such data. (Pernix.Br. at 33-34.) The reason is simple no such legal
requirement exists. See In Re: Copaxone Consol. Cases, 906 F.3d 1013, 1028
1
Of course, that motivation was also amply provided by the known liver toxicity
of acetaminophen. (Supra at 15.)
17
(Fed. Cir. 2018)
; Yeda Research v. Mylan Pharm. Inc.,
906 F.3d 1031, 1043 (Fed. Cir. 2018) (same).
Here, the District Court described ample reasons why a POSA would have
ts with
and without HI to provide a reasonable expectation that the Devane Formulation
could be administered without adjusting the starting dose. For example, a POSA
would have understood that the reason an HI study is conducted is precisely to
determine whether a dose adjustment is required, and that such adjustment is only
required if the pharmacokinetics in subjects with and without HI is sufficiently
different. (Appx80.) Thus, a POSA would have understood
I study to mean that no adjustment is required. (Id.,
Appx3649 (¶64).
denote a smaller quantitative difference than the 34 to 42% higher acetaminophen
blood level Jain reported for the subjects with moderate HI. (Id.
guidance on dose adjustments for HI patents states that adjustment should not be
recommended when the pharmacokinetic parameters are less than 1.25-fold
s (e.g., two-
disclose that an adjustment was not needed. (Appx80-81, Appx3573.)
18
Pernix argues that because labels for some other opioids with PK increases
between 1.4-fold and 1.95-fold for HI patients were split in recommending a dose
adjustment, a POSA would have only understood from Jai
less than 34% (1.34-
(Pernix.Br. at 35-36.) In making this argument, however, Pernix ignores that
Nucynta, the only product Pernix lists that does not require dose adjustment, had
the lowest PK increase at 1.4-fold. (Id.) Jain thus reported a lower PK increase
(less than 1.34-fold) for Vicodin CR than exhibited by Nucynta, and this would
only further confirm a
adjustment.
-supported by expert testimony.
Dr. Schmidt and Dr. Weinberger both testified that a POSA would understand Jain
as described above and would therefore have had a reasonable expectation of
success. (Appx80 (citing Appx779-780 (484:7-485:1), Appx781 (486:5-23),
Appx492-493 (197:1-198:22)).) Pernix complains that the District Court did not
credit Dr. Pernix.Br. at 35), but assessing
conflicting expert testimony is one of the basic functions of a trial court, and
Pernix has offered no basis on which to conclude that the District Court erred in
this regard. See Senju Pharm. Co. v. Lupin Ltd., 780 F.3d 1337, 1351 (Fed. Cir.
19
2015) (absent a compelling reason, appellate courts will defer to district courts in
weighing expert credibility).
Finally, Pernix appears to assert that the District Court erred in finding that
Jain provided a reasonable expectation of success because the PTO Examiner said
that there was unpredictability across different opioids, i.e., that the
pharmacokinetics for, say, oxycodone in patients with HI was not predictive of the
pharmacokinetics of, say, morphine. (Pernix.Br. at 32-33.) But, as the District
not evidence that one hydrocodone-containing product could not be used to predict
the pharmacokinetic parameters of another hydrocodone-
(Appx77.)
c. Data Is Relevant to the

Motivation to Combine Devane and Jain.
expectation of success because it is not obtained from subjects with HI.
(Pernix.Br. at 31.) This makes little sense. Devane describes a study comparing
the pharmacokinetics of single-ingredient hydrocodone formulations and a
combination hydrocodone-acetaminophen formulation. (Appx73-74, Appx3625
(¶¶103-105)
acetaminophen had no appreciable effect on the AUC0-inf
(Id.
20
something that would have a significant impact on the metabolism or the
-74 (quoting Appx551-552
(256:21-257:8)) speaks directly to the motivation to
combine Devane and Jain
look to Jain for guidance about the dosing of the Devane Formulation because
Pernix appears to fault the District Court for finding that the AUC data in
Devane was more relevant than its Cmax data because no witness explicitly stated
that at trial. (Pernix.Br. at 32.) Pernix cites nothing to suggest that a trial court is
restricted in its findings to propositions that have been uttered by a witness at trial,
however, nor can
pharmacokinetic study compared different dosage strengths of a single-ingredient
ER formulation to a combination IR formulation .
(Appx3625-3626 (¶¶103-105).) As the District Court explained, and as is self-
evident, an IR formulation will inherently provide a higher Cmax than an ER
formulation because it releases all of the active ingredient instantaneously rather
than gradually over time. (Appx73.) The Cmax data in Devane is therefore less
21
informative than the AUC data with respect to whether the presence of
acetaminophen affects the pharmacokinetics of hydrocodone.2
2. Findings Regarding
the IR Combination Products Are Correct.
a. Reliance on Vicoprofen Supports that
a POSA Would Look at the IR Hydrocodone Labels.
The District Court correctly found that a POSA would look both to Jain and
to the prior art labels for the IR hydrocodone combination products Vicodin and
use of the IR combination product Vicoprofen to demonstrate the safety and
efficacy of Zohydro ER (i.e., the Devane Formulation) in its new drug application
to FDA. (Appx75-
was no Vicoprofen data with HI
Pernix.Br. at 24-26.)
As an initial matter, Pernix again improperly attempts to characterize a
straight-
that findings regarding
2
That an elevated Cmax is more likely to be associated with adverse effects is
beside the point for the same reason. (Pernix.Br. at 32.)
22
Par Pharm., 773 F.3d at 1194,
1196.
In any event, the absence of HI data for Vicoprofen has no bearing on the
provides additional
support that a POSA would combine Devane and the IR hydrocodone labels.
(Appx75-78.) That follows from the simple fact that Zogenix used an IR
-ingredient
hydrocodone product.3 (Appx680 (385:18-21), Appx77.)
b. The Non-Prior Art Labels

Are Entitled to Little Weight.
Pernix contends th
(Pernix.Br. at 27.) The District Court
date from years after July 2012, the relevant priority date. (Appx62.) That is all
the more reasonable in view of the existence of the 2011 Vicodin label. (Appx47,
Appx3230-3233.) There should be no dispute that the version of the Vicodin label
3
The absence of specific HI data for the IR products is, if anything, only relevant
the Devane Formulation could be
successfully administered to patients with mild or moderate HI without dose
adjustment. In that regard, the District Court correctly
(Appx82.)
23
from the year before the priority date is more probative of the knowledge and
expectations of a POSA than a version that would not exist until years after the
priority date.
Pernix also mischaracterizes the District Court
HI as clear and convincing evidence that
Vicodin was known to be safe to administer to those patients without adjusting the
Pernix.Br. at 28.) In fact, the District Court made the nuanced
finding that a POSA reading the prior art labels
physician could prescribe a hydrocodone-containing product to a patient with
hepatic impairment, and . . . . [g]iven that the labels do not mention patients with
mild or moderate hepatic impairment, . . . might reasonably have concluded that it
would be safe to prescribe the same starting dose for such patients as for patients
clearly erroneous.
c. The District Court Correctly

Assessed Testimony.
Dr. abuse of ER opioids. (Pernix.Br. at 36
(citing Appx54-55).) But Dr. Gudin never testified that the sentence is not directed
at the risk of abuse. (See Appx994-995 (699:11-700:7).) Thus, the premise of
24
use of any opioid can cause over sedation and respiratory depression, this risk is
Pernix.Br. at 37.)
Finally, the case cited by Pernix, Apple Inc. v. Motorola, Inc., 757 F.3d
1286, 1316 (Fed. Cir. 2014), is far removed from the facts here. (Pernix.Br. at 37-
38.) In Apple, this Court held that it was error for a district court to exclude expert
concluded there was a better way to Id. at 1319. By
contrast, the District Court did not exclude any expert opinion; rather, it assessed
the evidence offered by Pernix through Dr. Gudin and found that it did not support
that an ER opioid product, when administered properly, would
present a greater risk of overdose than an IR product. (Appx54-55.)
indings Are Internally Consistent.
The District Court correctly found that a POSA would have been motivated
to administer the Devane Formulation to patients with mild or moderate HI without
adjusting the starting dose, and would have had a reasonable expectation of success
Those factual findings are well-supported by the
evidence presented at trial, somehow
25
the District Court findings is wrong. (Pernix.Br. at
18-23.)
1. The District s Factual Findings

Relating to Obviousness Are Internally Consistent.
Pernix first contends that the
for patients with mild or moderate HI is inconsistent with the finding that a POSA
would have been motivated to administer the Devane Formulation to such patients
without adjusting the starting dose. (See Pernix.Br. at 18-19 (quoting Appx59).)
ignores the different scope and context of the two findings.
Whereas the first finding is specific to Smith and Johnson, articles directed to
opioid dosing generally (see Appx55-59), the second is based on the prior art as a
whole, including the hydrocodone-specific prior art Jain and the IR hydrocodone
labels. (See Appx75-84.) Indeed, the District Court specifically explained that
suggests that a physician must always adjust the dose
of hydrocodone for patients with mild or moderate [HI] (Appx59.) And, as the
District Court correctly found, Jain and/or the IR hydrocodone labels would have
given a POSA reason to conclude that it would be safe to use the same starting
as in patients without HI. (Appx70-71.)
26
Pernix
finding that there was a reasonable expectation of success with an
unadjusted dose and the finding that a POSA would be cautious in administering
opioids to patients with HI. (Pernix.Br. at 18-19 (citing Appx53).) As an initial
matter, there is no conflict between expecting that the starting dose does not
in dose recommendations. A cautious
physician aims to prescribe the correct dosage amount, which for the Devane
Formulation is an unadjusted dose in patients with mild or moderate HI.
Furthermore, the District Court made the finding
generally. (See Appx50, Appx53.) It explained that these articles are
representative of some of the knowledge that a person of ordinary skill would
(Appx53 (emphasis added).) That is entirely consistent
with the finding that the prior art as a whole, including the hydrocodone-specific
prior art, provided the POSA with a reasonable expectation that the Devane
Formulation could be safely administered without dose adjustment.
Pernix
Acetaminophen Communication and other FDA documents in its obviousness
its lack of reliance on the fact that FDA
required Cephalon to perform an HI study for its ER hydrocodone product.
27
Cephalon [because the] standard to
find a motivation to combine is far below what is sufficient to prove safety and
efficacy to the FDA (Appx77.) Tellingly, Pernix does not even attempt to
explain why . After all, it is self-evident
that different facts may have different significance to an obviousness analysis,
even if arising out of the same federal agency. Here, there is no tension between
the tringent than an
obviousness standard and its finding that the FDA Acetaminophen Communication
would have motivated a POSA to reduce or eliminate acetaminophen from ER
medications.
2. Pernix Misrepresents the Standard for Reasonable

Expectation of S estimony.
Pernix next contends that the District C finding of reasonable
expectation of success
POSA could hypothesize, , profile of a
hydrocodone product based on Jain. (Id. at 21.) Pernix is wrong. This Court has
on many occasions explained that
Pfizer, 480 F.3d at 1364. Indeed, the case law is clear
that obviousness cannot be avoided simply by a showing of some degree of
unpredictability in the art so long as
28
Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1292 (Fed. Cir. 2013). See also In re
Droge, 695 F.3d 1334, 1338 (Fed. Cir. 2012) Obviousness does not require
4
absolute predictability of success . . . .
Furthermore, Pernix ignores critical portions of Dr. Schmidt . In
the
, Dr. Schmidt
explained that his answer in the negative merely meant that
percent certain. Appx594-595 (299:16-300:6).) He also expressly testified that
his use of the term
(Appx637 (342:9-17)), and
-only product would not need dose
adjustments in patients with mild or moderate HI. (Appx541-542 (246:8-247:8).)
4
Pernix points to the statement in DePuy Spine, Inc. v. Medtronic Sofamor Danek,
Inc., 567 F.3d 1314, 1326 (Fed. Cir. 2009)
(Pernix.Br. at 22.) That dicta was derived from the Supreme
he combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results. DePuy Spine, 567 F.3d at 1326 (quoting KSR Int'l Co. v. Teleflex Inc.,
550 U.S. 398, 416 (2007). The Federal Circuit has explained that KSR
longstanding focus on . Institut

Pasteur & Universite Pierre Et Marie Curie v. Focarino, 738 F.3d 1337, 1344
(Fed. Cir. 2013)
reasonable expectation of success and not some higher level of certainty.
29
Thus, there is no inconsistency, and Dr. s testimony supports the District

5
C
3. The District Findings Relating to Written

Description and Obviousness Are Fully Consistent.
the District Court written
description findings somehow conflict with its obviousness findings. (Pernix.Br. at
22-23.) The District Court found both that: (1) the prior art would not have
provided guidance as to which of the formulations described in the Asserted
Patents, other than the Devane Formulation, would fall within the functionally-
claimed genus (Appx105); and (2) Jain and the prior art IR hydrocodone labels
provided guidance as to the dosing of the Devane Formulation in patients with HI
(Appx78). These findings are not in conflict because they were made in different
legal contexts and answer different questions.
5
Sanofi v. Watson Labs., Inc., 875 F.3d 636 (Fed. Cir. 2017)
and
is also misplaced. (Pernix.Br. at 21, 27.) In Sanofi, this Court affirmed a finding
that the prior art did not provide a reasonable expectation of success because the
relied-upon prior art statement was based on a non-concrete, post-hoc analysis.
875 F.3d at 647-49. And in Genzyme
was insufficient because, overall, the
prior art was directed to a different purpose. 716 F. Here, Jain
reports the results of an actual (not post-hac) HI study demonstrating that dose
adjustment would not be required. (See Appx1064 (769:11-15).)
30
The written description question was whether the Asserted Patents disclosed
structures known to correspond to the functional claim limitations namely the PK
Limitations and Non-Adjustment Limitation. (Appx105 (citing Amgen Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1332 (Fed. Cir. 2003).) The District
Court correctly found that, unlike in the Amgen case, the art would not have
informed a POSA that structures disclosed in the Asserted Patents correspond to
the functional limitations. (Id.) Indeed, Pernix does not contend that any prior art
presented at trial provided such information (Pernix.Br. at 22-23), and its expert
Dr. Koleng admitted that he had not even been asked to consider what formulation
attributes are responsible for the functional limitations. (Appx98-99, Appx932
(637:18-24).) The obviousness question, by contrast, was whether Jain and/or the
IR hydrocodone labels would have provided a POSA with a reasonable
expectation that the Devane Formulation would not require a dose adjustment in
patients with mild or moderate HI. A reasonable expectation of success does not
require a POSA to know the underlying structure giving rise to the claimed results;
rather, and as the District Court found, it is sufficient that Jain disclosed that an ER
hydrocodone formulation did not require adjustment (Appx79-80), and that the IR
(Appx82).
Pernix also contends that the District Court
[ed]
31
(Pernix.Br. at 22.) As
already discussed, however, this Court has repeatedly explained that a finding of a
reasonable expectation of success does not require absolute predictability in the art.
Supra at 29.
between the
District Court
even if Pernix could have identified such an inconsistency, that in itself could not
demonstrate that the factual finding with respect to obviousness is clearly
erroneous.
The District Court Correctly Applied

Inherency Principles in Its Obviousness Analysis.
Pernix argues that the District Court erred in finding that the PK Limitations
are inherently disclosed in the Devane Formulation because Devane does not
disclose administering its formulation to patients with mild or moderate HI.
(Pernix.Br. at 37-38.) s flawed because it focuses
exclusively on Devane, whereas the prior art at issue is the combination of Devane,
Jain, and/or Vicodin and Lortab.
This Court has held that inherency applies in the obviousness context where
Par Pharm., 773 F.3d at 1195. Here, Jain, Vicodin, and Lortab all
disclose administration of a hydrocodone-containing dosage form to mild or
32
moderate HI subjects. (Appx70.) The District Court correctly concluded that a
POSA would have been motivated to combine Devane and these prior art
references (see supra at 14-17, 22-23), and thus to administer the Devane
Formulation to mild or moderate HI subjects. (Appx71.) That administration the
product of combining prior art elements
values recited in the claims. Par Pharm., 773 F.3d at 1195. Accordingly, the
District Court in its inherency
analysis.
Pernix cites three cases, but they are all distinguishable from Par
Pharmaceuticals and from this case. (Pernix.Br. at 37-38.) In the first two cases,
In re Oelrich, 666 F.2d 578, 581 (C.C.P.A. 1981) and Perricone v. Medicis Pharm.
Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005), the prior art disclosures in those
cases did not necessarily result in the claimed features. Moreover, those cases
relate only to inherent anticipation not inherency in the obviousness context
and thus do not address instances where a combination of prior art elements
naturally results in a limitation that is not expressly disclosed. case,
Endo Pharm. Inc. v. Teva Pharm. USA, Inc.
(non-precedential), addresses inherency in an obviousness analysis but is readily
distinguishable, as the District Court explained:
The [Endo] court explained that because give

any indication to a person of ordinary skill that oxymorphone could
33
have been developed into a controlled release formulation providing

effective analgesia over a twelve-hour period, the pharmacokinetic
result of the combination of elements explicitly disclosed by the prior

Id. at 971 (quoting Par Pharm., 773 F.3d at 1195-96). In this
case, by contrast, the formulation recited in the claims was explicitly
disclosed by Devane, and the pharmacokinetic limitations were
necessarily present in, and a natural result of the administration of,
that formulation.
(Appx68-69 n.11 (quoting Endo ).) Pernix does not even
attempt to rebut the District Court analysis.
The District Court Properly Considered the Objective Indicia.

1. The District Court Did Not Reach Its Conclusion on
Obviousness Prior to Considering the Alleged Indicia.
Pernix asserts that the District Court found obviousness in Section III.C. of
its opinion
(Pernix.Br. at 38-39.) Even a cursory review of the District Court opinion,
however, is without basis. In the final
sentence of Section III.C, immediately prior to discussing secondary
considerations, the District Court
reasonab -release hydrocodone
bitartrate could be administered to patients with mild or moderate hepatic
impairment without adjusting the starting dose. (Appx84.) There is no
conclusion as to the ultimate question of obviousness. (Id.) On the contrary, the
first sentence of the next section states that
34
can support a finding of nonobviousness (Id.) The District Court thus
considered the indicia as part of its obviousness analysis.
The case Pernix cites, In re Cyclobenzaprine Hydrochloride Extended-
Release Capsule Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012), is inapposite.
There, this Court held that the district court erred because it shifted the burden of
persuasion to the patentee once it found that the defendants had proved a prima
facie case of obviousness. Id. at 1075. By contrast, Pernix does not and cannot
contend that the District Court imposed on it a burden of persuasion as part of the
obviousness analysis.
2. The District Court Properly Assessed

Allegation of Failure of Others.
Pernix contends that the District Court should have assigned greater weight
to the non-prior art label for Vantrela, which states that dose adjustment is required
for patients with mild or moderate HI. (Pernix.Br. at 39-40. only
support for this proposition is attorney argument that, if the prior art would have
motivated a POSA to administer ER hydrocodone-only formulations generally to
HI patients without adjustment, then a POSA would have administered Vantrela
without adjustment, subjecting HI patients to potential harm. (Id.) This argument
does not come close to demonstrating clear error.
35
The District Court appropriately considered the Vantrela
in the context of the success of the prior art Vicodin CR formulation and the
contemporaneous Hysingla ER formulation, each of which can be administered to
patients with mild or moderate HI without dose adjustment. (Appx87-88.) Pernix
offers no reason or legal support to show that a single instance of failure when
others succeeded should be entitled to more weight than given by the District
Court.6
the District Court erred by relying on Hysingla ER
is also misguided. (Pernix.Br. at 40.) The Hysingla ER study report is dated
May 23, 2013 (Appx1803), and Dr. Gudin admitted that the Hysingla ER
researchers had obtained the data from the pharmacokinetic study, which showed
that dose adjustment was not required, by November 2012. (Appx1090 (795:1-3).)
Thus, the success of Hysingla ER was realized between 12 and 18 months after the
named inventors reduced the claimed methods to practice. (Appx3668.) This
a year later than the earliest possible
reduction-to-practice date of the claimed invention, qualified as a simultaneous
6
Pernix cites Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530 (Fed. Cir. 1983) for
support, but that case does not even relate to failure of others. (Pernix.Br. at 39.)
There, the district court completely failed to include secondary considerations in its
analysis. Stratoflex, 713 F.2d at 1538-39.
36
, 618 F.3d 1294, 1306
(Fed. Cir. 2010).
In the case cited by Pernix, the Court found that independent development
that occurred filing date
was too late to qualify as simultaneous invention. Ransomes, Inc. v. Great Dane
Power Equip., Inc., 232 F.3d 911 (Fed. Cir. 2000) (unpublished) (emphasis added).
Presumably, however, the invention there occurred prior to the submission of the
patent application. See Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d
1367, 1380 n. 4 (Fed. Cir. 1986) (no simultaneous invention when it occurred
Thus, Ransomes does not stand for the rigid proposition
that independent development must occur within one year of the claimed invention
to be probative of obviousness. In any event, even if the success of Hysingla ER
were not deemed probative, the success of Vicodin CR alone demonstrates that the
District Court did not clearly err in assigning little weight to the alleged failure of
Vantrela ER.
3. The District Court Correctly Found No Unexpected Results.
As the District Court
there is a difference between the results obtained and those of the closest prior art,
and that the difference would not have been expected by one of ordinary skill in
37
the art at the time of the inventio (Appx86 (quoting Bristol-Myers Squibb Co.
v. Teva Pharm. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014)).) There can be no
question that Jain (in addition Devane itself) is the closest prior art here (see, e.g.,
Appx2980 (Examiner stating that Jain, then called Rita, is the closest art)), and
Pernix does not contend otherwise on appeal. (See Pernix.Br. at 40-42.) The
District Court
Dr. was unsupported. (Appx84.)
Pernix does not challenge the District Court
considering Jain, would not have found it unexpected that dose adjustment was not
required for patients with mild or moderate HI. (Pernix.Br. at 40-42.) Rather,
Pernix complains that the District Court should hav
Id.) The District
Court in that regard are well-supported by the evidence, however, and
Pernix does nothing to show that they are somehow clearly erroneous. For
example, Pernix does not dispute the finding that there was no evidence that the
named inventors were aware of the HI study reported in Jain, the closest prior art,
and that their testimony about the putative unexpected results was therefore
entitled to less weight. (Appx86.) The District Court also expressed skepticism of
38
their own patents,7
(Appx86-87 n.15
(quoting Tyco Healthcare Grp. LP v. Mut. Pharm. Co., 642 F.3d 1370, 1377 (Fed.
Cir. 2011)).)
In sum, the District Court
unexpected results are well-supported by the record evidence. Pernix provides no
basis to conclude they are clearly erroneous.
E. The District Court Did Not Misinterpret the Asserted Claims.

Pernix final argument on obviousness is that the District Court
Nucynta requiring an
adjustment for patients with moderate HI, but not mild HI, would satisfy the no-
(Pernix.Br. at 42-43.) In fact, the District Court simply
noted that the Asserted Patent description of the Nucynta label was quite
selective and omitted the fact that Nucynta does not require dose adjustment in
patients with mild HI. (App86.)
7
Pernix contends that the named inventors have no interest in the validity of the
Asserted Patents because they assigned their rights to Pernix. (Pernix.Br. at 41.)
But assignees often retain pecuniary interest in the validity of the patent, and
typically accrue indirect monetary and non-monetary benefits from being a named
inventor on a valid patent.
39
dose adjustment in patients with mild or moderate HI. (Appx83-84.)
the District Court did not find that an ER
hydrocodone formulation that requires dose adjustment only in patients with
moderate HI could anticipate the Non-Adjustment Limitation. Such a finding
would, however, have been correct. or
can only be invalidated by the use
of a formulation that does not require adjustments for both patient groups is belied
by basic principles of patent law. See, e.g., In re Theresa
(Fed. Cir. 2018) (unpublished) (holding cla
-set words or pre- obvious where
of pre- (emphasis in
original). As Pernix itself admits,
and Pernix.Br. at 42.) The claims are thus rendered invalid if it
were obvious to practice the methods with respect to patients with either mild or
moderate HI. Chapman v. Casner 294, 297 (Fed. Cir. 2009)
40
8
This point is of little
significance, however, and does not impact this review in any way.
In summary, the District Court
are invalid for obviousness is based on well-supported factual findings regarding a
combine, reasonable expectation of success, and objective
indicia. Pernix has not come close to demonstrating that those factual findings are
clearly erroneous, and this Court should therefore affirm the District Court
obviousness conclusion.
II. THE DISTRICT COURT CORRECTLY

HELD THAT THE ASSERTED CLAIMS ARE
INVALID AS LACKING WRITTEN DESCRIPTION.
exclude, as set forth in the claims, does not overreach the scope of the invent
Ariad, 598
F.3d at 1353-54. The Asserted Claims exemplify this overreach. The named
he PK results
8
To the extent Pernix is now asserting tha -
Two-Step Claims is a limitation on the properties of the administered formulation
i.e., a requirement that the formulation intrinsically requires no adjustment for
both patients with mild HI and patients with moderate HI that argument directly
contradicts what Pernix told the District Court when arguing that Devane does not
inherently anticipate these claims. Pernix stated in post- -
adjustment limitation . . . is not a property, but rather
n.6 (emphasis in original).) Pernix cannot have it both ways.
41
of an FDA-mandated HI study, that the Devane Formulation did not require a dose
adjustment for patients with mild or moderate HI. The alleged contribution is thus
limited to observations concerning the Devane Formulation. By contrast, the
Asserted Claims cover administration to mild and moderate HI patients of all
hydrocodone-only ER oral dosage forms that either meet the recited PK parameters
or do not require a dose adjustment.
The District Court alid for lack of
adequate written description follows from this fundamental disconnect between the
narrow alleged contribution to the art and the genus of
formulations they have claimed. (Appx101.)
assessing written description support for genus claims, see AbbVie Deutschland
GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014),
the District Court made well-supported factual findings that the specifications do
not disclose either a representative number of species or structural features that
would enable a POSA to visualize or recognize members of the genus. (Appx101-
109.)
As set forth below, this Court should affirm the finding of inadequate written
description because the District Court: (A) properly determined that the Asserted
Claims are genus claims; (B) made factual findings strongly supported by the
evidence; (C) correctly distinguished cases
42
functionally-claimed genera; and (D
arguments.
A. s Are Based on a
Reading of the Claims that Is
possessed the claimed
invention (Pernix.Br. at 44) is based on a misreading
As the District Court
acknowledge . . . is that it has claimed not just the [single working] formulation
disclosed in the common specification, but any formulation that will work to
produce the results recited in the claims (Appx108.) This failure is fatal to
The Asserted Claims are genus claims. [T]he formulation limitations
recited in the claims read on all oral dosage units comprising extended-release
(Appx90.)
The other limitations in the asserted claims are all functional in natu
not inform a [POSA] as to what the formulations must contain in order to exhibit
(Id.)
The District Court described the genus of formulations potentially covered
expert Dr. Mayersohn testified that
-only dosage forms,
43
including liquids such as suspensions, syrups, solutions and emulsions, and solids
such as tablets (single, double, or triple-layer), capsules and lozenges, and may
involve pellets, beads, ion exchange and more. (Appx849-850 (554:13-555:9).)
Koleng also admitted that the claimed genus could encompass
matrix, pulsatile and osmotic pump dosage forms, and that, within those categories
of dosage forms, formulators may use scores of excipients in various amounts as
binders, disintegrants, and lubricants. (Appx943-947 (648:19-653:13).) Indeed,
the patents disclose an extensive, non-exhaustive list of suitable excipients.
(Appx2799-2800 (18:44-19:44).) For just one category of excipients, plasticizers,
the patents identify 41 suitable types of excipients. (Appx2800 (19:30-44).)
The Asserted Claims are thus broadly cast in generic form: they recite a
broad genus of ER hydrocodone-only formulations that is only functionally
defined.9
Ariad, 598 F.3d at 1351.
patent claims a genus using functional language to define a desired result, the
9
Each of the asserted claims recites the functional limitations that (1) the starting
dose administered to patients with mild or moderate HI is not adjusted relative to a
patient without HI, and/or (2) the dosage unit provides certain hydrocodone release
profiles defined by the AUC and/or Cmax observed in patients with mild or
moderate HI. (See, e.g., Appx2802-2803 (23:66-26:35).)
44
specification must demonstrate that the applicant has made a generic invention that
achieves the claimed result and do so by showing that the applicant has invented
species sufficient to support a claim to the functionally- AbbVie,
759 F.3d at 1299 (quoting Ariad, 598 F.3d at 1349).
Pernix argued before the District Court that its claims were not generic, and
the District Court
appeal, Pernix does not directly dispute that conclusion and even acknowledges in
passing that its claims cover a genus. (Pernix.Br.

10
Instead, Pernix
inapposite. (Id. at 62.) As the District Court recognized, however, this argument is
premised on misreading the Asserted Claims as narrower claims that do not cover a
genus. (Appx91-92.) The named inventors chose not to limit their claims to a
method using the Devane Formulation. Instead, they
10
Pernix sprinkles statements throughout its brief intended to imply that the
Asserted Claims cover a species rather than a genus, stating, for example, that the
cover a method of treating only HI patients with a specific dose, using a
particular formulation that is ER and contains hydrocodone as the only active
(Pernix.Br. at 53-54 (emphasis added).) Of course, the claims are not
any ER hydrocodone-only formulation
that achieve the claimed function.
45
none of which (except for the Devane Formulation) has been shown to satisfy the
11
(Id.)
In an attempt to distinguish the numerous cases addressing genus claims,
Pernix cites Amgen for the proposition that the written description requirements are
(Pernix.Br. at 62.) But the
Court in Amgen made clear that the written description question for functionally-
to a particular, known structure. Amgen, 314 F.3d at 1332. As discussed in the
section that follows, the District Court correctly concluded that neither the
specifications nor the prior art disclosed such a correlation.
B. The District Court Correctly

Found that the Specifications Do Not
Demonstrate Possession of the Claimed Genus.
To provide adequate written description support for genus claims, a patent
either a representative number of species falling
within the scope of the genus or structural features common to the members of the
11
Although Pernix implies that its claims have sufficient written description
because they are method claims (Pernix.Br. at 56 (emphasizing the word
attempts to distinguish method claims
from composition of matter claims. Univ. of Rochester v. G.D. Searle & Co., 358
F.3d 916, 926 (Fed. Cir. 2004) (rejecting argument that cases directed to
composition of matter claims are distinguishable from the method claims at issue
46
genus so that one of skill in the art can visualize or recognize the members of the
Ariad, 598 F.3d at 1350 (internal quotations omitted). See also AbbVie,
759 F.3d at 1299 (same); In re Alonso, 545 F.3d 1015, 1019 (Fed. Cir. 2008);
Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568-69 (Fed. Cir.
1997). The District Court made factual findings that the specifications did not
disclose either a representative number of species or structural features common to
the genus. Pernix never acknowledges this standard, and it does not come close to
proving clear error. See Regents, 119 F.3d at 1566 (stating that written description
presents a question of fact reviewed for clear error).

a Representative Number of Species.
The District Court concluded that the Asserted Patents disclose only a single
operative species (the Devane Formulation tested in Example 8) that falls within
the genus of ER hydrocodone-only dosage forms covered by the Asserted Claims.
(Appx97.) This Court has repeatedly held, including when addressing method
claims, that possession of one species or one type of species was insufficient to
show possession of a claimed genus. AbbVie, 759 F.3d at 1299-1300; Alonso, 545
F.3d at 1021.
representative is particularly appropriate given the evidence offered at trial
pointing to the variety of hydrocodone-only ER formulations that the Asserted
Claims potentially cover. (See supra at 43-44.)
47
Pernix relies heavily on
or formulations (Pernix.Br. at 45, 50), but the
District Court correctly concluded that these 377
. (Appx100.) In fact, the
specifications do not disclose that these formulations would practice any of the
Asserted Claims. (Id.; Appx854 (559:1-16).)
conclusion. He admitted that in order to determine whether any of these
more of the Asserted
Claims, a POSA would need to do the same work that the named inventors did and
perform an HI study. (Appx959-961 (664:22-666:20), see also Appx856 (561:9-
23).) Thus, as the District Court determined, these formulations are not
representative of the Asserted Claims because no one not the inventors, not
knows if these 377
formulations would actually practice the Asserted Claims.12 (Appx99, Appx675
(380:6-11), Appx696 (401:11-13), Appx731-732 (436:24-437:8), Appx959-961
12
Accordingly, the District Court did not place the burden on Pernix to
Pernix contends. (Pernix.Br. at 50.) The District Court instead concluded from the
t the specifications did not
disclose that these formulations actually practiced the Asserted Claims.
48
(664:22-666:20).) Accordingly, even though
are structurally similar to the Devane Formulation, the specifications do not
contain sufficient disclosure to enable
from non- Rochester, 358 F.3d at 926.
Even if a POSA
were to assume that the relative similarities between the Devane Formulation and
the other 377 formulations make the
Claims, the claims would still lack adequate written description because the
AbbVie, 759 F.3d at
1300. In AbbVie, Id.
Nevertheless, the claims
described species are all of the similar type and do not qualitatively represent other
Id.
The same is true here. The
covered by the claimed genus number of other
formulations with structural characteristics (e.g., matrix, pulsatile and osmotic
dosage forms) that are very different from the Devane Formulation. (Appx90;
supra at 43-44.)
49
(Appx960-961 (665:14-666:20 (Dr. Koleng admitting that, given
).) Accordingly, the named inventors have
possess. AbbVie, 759 F.3d at 1300.
Pernix attempts to distinguish AbbVie by pointing to evidence in that case of
undisclosed species with differing characteristics, apparently contending that
Alvogen should be required to prove the existence of such species. (Pernix.Br. at
63.) The District Court properly rejected this argument
patentee may not draft claims that are sweepingly broad and then defend against a
challenge to their breadth by pointing out that the challenger has failed to show
that there are any operative embodiments within the broad scope of the claims
10.) That would be tantamount to
(Appx110.)
Moreover, the District Court credited evidence that Hysingla ER practices
the Asserted Claims despite having different formulation characteristics. (Id.)
Pernix repeats the argument it made below that Alvogen purportedly waived any
reliance on Hysingla ER (Pernix.Br. at 64), but Pernix opened the door to this
evidence by arguing for the first time at trial that an IR component was a common
structural characteristic that defines the claimed genus. Hysingla ER, however,
50
establishes that a hydrocodone product with only an ER component can be covered
by the Asserted Claims: the hydrocodone in Hysingla ER is contained in an inner
core and an outer shell, both of which contain a well-known controlled-release
excipient, polyethylene oxide. (Appx5014 (11:17-31, 11:50-53, Formulation M in
Table 14), Appx1798-1801 (disclosing that the formulation for Hysingla matches

Structural Features Common to the Claimed Genus.
The second option for showing adequate written description of genus claims
using functional language is to disclose
members of the genus so that one of skill in the art can visualize or recognize the
Ariad, 598 F.3d at 1350 (internal quotations omitted).
Here, the District Court made factual findings that
any evidence offered at trial points to any structural features that would assist a
[POSA] in identifying species falling within the asserted generic
(Appx98.) Pernix has not shown any error in the District Cour
alone any clear error.
structural characteristics and preferred amounts of excipients, and the District
jects. (Pernix.Br. at 60-
51
62.) What the District Court actually credited, however, was
description of what was disclosed in the examples, tables and figures of the
9.) The District Court expressly declined to credit
the opinions that Dr. Koleng offered based on those disclosures
specification would provide guidance to a [POSA] regarding how to make a
formulation that would satisfy the limitations of the asserted claims, except for the
Devane formulation set forth in Example 8 or compositions closely similar to that
one. (Id.) In fact, Dr. Koleng admitted that he did not consider what specific
attributes of the Devane Formulation resulted in the claimed functional limitations.
(Appx98 (quoting Appx932 (637:18-24)).) Nor was Dr. Koleng
on what specific special sauce, if you will, in the formulation resulted in the PK
profile. (Id.) As the District Court observed, a
POSA could
the considerable qualification that the task
of determining which formulations would work for that purpose would require
clinical hepatic impairment testing of each formulation (Appx99.) Pernix simply
ignores that qualification.
Pernix also ignores the testimony of Mayersohn on
these factual issues. Dr. Mayersohn is a PK expert who has done studies in
subjects with HI. (Appx877 (582:3-12).) By contrast, Dr. Koleng is not a PK
52
expert (Appx950-951 (655:23-656:4)) and did not point to any experience
targeting PK values in HI subjects. Moreover, Dr. Mayersohn gave testimony that
4) on critical points:
not disclose
what combination of components would give rise to the target
(Appx93 (citing Appx859 (564:8-14).)
[T] presentation of
structural or formulation characteristics that would allow a person of skill
(quoting Appx858 (563:11-16)).)
The District Court thus had good reason to credit Dr. M
it was not clear error for it to do so. See Senju, 780 F.3d at 1351.
Pernix regarding the pharmacokinetic data and dissolution
profile for the Devane Formulation disclosed in the Asserted Patents similarly have
no merit. First, such data are not structural in nature and thus do not constitute
mon to the members of the genus that would satisfy the
written description requirement. Ariad, 598 F.3d at 1350. Second, Pernix cannot
point to any disclosure in the specifications, for example, that hydrocodone-only
ER oral dosage forms having similar dissolution profiles will practice the Asserted
Claims or that such dosage forms having substantially different dissolution profiles
would not practice the Asserted Claims. The disclosure that one
hydrocodone-only ER dosage form with those PK and dissolution profiles
53
practices the claims does not demonstrate possession of the claimed genus.
Formulation produced similar PK results in HI and non-HI subjects is further
evidence that the specifications do not disclose any structural or other properties
that are common to the claimed genus. (Appx98 (citing Appx675 (380:6-11),
Appx696 (401:11-13), Appx731-732 (436:24-437:8)).) Pernix criticizes the
District C (Pernix.Br. at 47-48), but the
cases Pernix relies on are inapposite because they do not concern functionally-
d for such claims.
Had the named inventors limited their claims to the Devane Formulation rather
than a genus about inventor testimony might have merit. But
because the named inventors claimed a genus, their lack of understanding as to
why the single species they tested produced the results it did is further proof that
they did not possess the genus they have claimed.
C. The District Court Correctly Applied
properly determined that the Asserted Claims
non-
those findings. This Court requires that specifications supporting such claims
disclose a representative number of species or structural features common to the
54
genus. The District Court made factual findings that the specifications here did not
contain either disclosure. Pernix does not attempt to show that those factual
findings were clearly erroneous, nor could it.
Instead, Pernix presses forward with arguments based on case law that does
not concern functionally-claimed genera. None of this case law provides a basis to
disturb the District Court findings.
1. Feutterer and Herschler Are Distinguishable

Because They Are Directed to Different Types of Claims.
The claims at issue in In re Fuetterer, 319 F.2d 259 (C.C.P.A. 1963) and In
re Herschler, 591 F.2d 693 (C.C.P.A. 1979), are different from the ones here and
dictate a different result on written description. In Fuetterer, the claims recited a
combination of rubber, other materials and an inorganic salt capable of holding
materials in colloidal suspension in water that produces an improved tire tread.
319 F.2d at 260-61. The specification stated that any inorganic salt that maintains
a colloidal suspension was suitable. Id. at 265. In Herschler, the claims recited a
method of improving topical administration of steroidal agents by combining the
agent with dimethyl sulfoxide. 591 F.2d at 695. In each case, the specification
disclosed limited examples of an element of the combination (inorganic salts or
steroidal agents), but the court found the claims to have adequate written
description because the particular inorganic salt or steroidal agent used was
. Herschler, 591 F.2d at 700-701; see also Fuetterer,
55
319 F.2d at 265
The District Court properly distinguished Fuetterer and Herschler. The
alleged invention here is not that all hydrocodone-only ER oral dosage forms yield
certain PK profiles or do not require dose adjustment in HI subjects. Instead, the
named inventors have claimed some functionally-defined subset of hydrocodone-
only ER oral dosage forms. But they have not explained what that subset is other
than that it includes dosage forms that perform the recited functions. As the
District Court recognized,
with a formulation that performs the recited functions does little more than to say
that the method of treatment is effective with a
(Appx103.)
Pernix further objects to the District Court analysis of Fuetterer by
claiming that it , but Pernix
makes the same mistake that the appellant did in a case Pernix cites: Cooper
Cameron Corp. v. Kvaerner Oilfield Prods., Inc., 291 F.3d 1317, 1322-23 (Fed.
Cir. 2002). (Pernix.Br. at 56-57.) The District Court [i]dentifying
the formulation is essential to the invention because the Asserted Claims cover
some but not all formulations that meet the recited structural limitations.
(Appx103.)
56
specifications to
that the inventors have invented the full scope of the formulations recited in the
claims and not simply a single operative embodiment within that class Id.) The
District Court d a legal test, just as this
Court did not announce a new legal test when it used the same word in Gentry
Gallery, Inc. v. Berkline Corp., 134 F.3d 1473, 1479-80 (Fed. Cir. 1998). See
Cooper Cameron, 291 F.3d at 132
Moreover, the District Court
is Court has found fault with an
Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1565 (Fed. Cir. 1991). In this case, the
District Court to give effect to the claim language; it is
Pernix that seeks, improperly, to re-cast its claims more narrowly. (See, e.g.,
Pernix.Br. at 56 (arguing that the inventors demonstrated possession via Example
8, where that Example shows only that the Devane Formulation practices the
Asserted Claims).)
2. Alcon Concerns Different

Types of Claims and Different Issues.
Pernix expends much ink asserting that the District Court committed legal
error by reaching a different result than in Alcon Research Ltd. v. Barr Labs., Inc.,
57
745 F.3d 1180 (Fed. Cir. 2014) (Pernix.Br. at 46-54), but the case is easily
distinguishable for some of the same reasons identified above.13 As in Fuetterer
and Herschler, the claims at issue in Alcon involved a combination of a
prostaglandin (a class of drug) with a PECO to
enhance the chemical stability of the prostaglandin. 745 F.3d at 1183 (quoting
Claim 1, ically-stabilizing amount
of a [PECO] to [a composition comprising a therapeutically-effective amount of a
. The appellee argued that the specification only demonstrated
operability with a single prostaglandin. Id. at 1190. But as this Court explained in
rejecting that argument
proven to the skilled reader that the invention works Id. at 1191.
This case presents a different issue. The named inventors do not claim that
all hydrocodone-only ER oral dosage forms practice the claims. Instead, the
some hydrocodone-only ER oral
dosage forms having the recited PK profiles or not requiring a dose adjustment in
13
Alcon, Pernix -trial brief discussed Alcon more than
Alcon in that brief spans only one paragraph directed to a narrow issue and two
secondary cites in the 13 pages devoted to written description. (Appx1470-1472,
Appx1478-1479.) In any event, the District Court considered Alcon and even cited
it. (Appx108.)
58
HI subjects and other such dosage forms not meeting the functional requirements.
The specifications do not tell POSAs which formulations, other than the Devane
Formulation, can achieve the specific PK values without conducting an HI study.
(Appx856 (561:16-23), Appx858-860 (563:3-565:2), Appx949 (654:10-18).) The
named inventors possessed only a single operative species and, as the District
Court recognized, merely defined the genus they claimed
The identity of the hydrocodone-only ER formulations that
fall within the Asserted Claims is unknown. See Rochester, 358 F.3d at 926
(claims lack written description if POSAs cannot readily distinguish infringing
from noninfringing compounds or methods).
disclosed in Alcon to the lone example disclosed in the Asserted Patents does not
advance its argument. (Pernix.Br. at 49.) This Court has repeatedly held that one
species is insufficient to support a functionally-claimed genus. AbbVie, 759 F.3d
at 1299-1300; Alonso, 545 F.3d at 1021. The Court in Alcon was not addressing
claims directed to a functionally-claimed genus, and there was no evidence that a
Alcon, 745
F.3d at 1191-92. For those reasons, it is of little moment that the specifications in
Alcon demonstrated operability with only a single working example. As recounted
59
above, and in sharp contrast to Alcon, there was ample evidence in this case to
support the District Court did not
possess the claimed genus.
3. Union Oil Is Inapposite.

Pernix also points to Union Oil Co. of Cal. v. Atlantic Richfield Co., 208
F.3d 989 (Fed. Cir. 2000) (Pernix.Br. at 59-62), but it is readily distinguishable.
The claims in Union Oil recited a gasoline with specific chemical properties.
Union Oil, 208 F.3d at 992. Skilled artisans knew how to formulate gasoline with
such properties by mixing petroleum stocks,
invention in terms of various characteristics also inform those of skill in the art of
Id. Here, by contrast, Dr. Koleng
admitted that a POSA would not even have known whether the so-called
let alone any other
ER hydrocodone formulations practice the functional limitations of the Asserted
Claims. (Appx959-961 (664:22-666:20).)
D.
Pernix equally meritless. Alvogen did not have a
burden to prove that there are other ER hydrocodone-only formulations that are
inoperable, as Pernix suggests. (Pernix.Br. at 50.) Pernix cites the Alcon
finding that the party asserting invalidity failed, in the context of enablement, to
60
(Pernix.Br. at 50
(quoting Alcon, 745 F.3d at 1089-90).) Written description presents a different
question, however, as the Alcon Court separately discussed. Alcon, 745 F.3d at
1090-92.
Pernix also
Pernix.Br. at 51), but the
District Court said no such thing. Rather, the District Court recognized that the
Asserted Claims potentially cover other formulations that lack structural
characteristics such as an 80:20 ratio of ER to IR components (Appx91-92), and
rejected Pernix -write the claims to cover only the
Devane Formulation (Appx110). In other words, the District Court properly
refused importing structural limitations
from the specification (id.), which is much different from declaring those
CONCLUSION
For the reasons set forth above, this Court should affirm the District C
judgment that the Asserted Claims are invalid as obvious and lacking written
description.
61
Respectfully submitted,
/s/ Chad A. Landmon

Matthew J. Becker
Chad A. Landmon
Edward M. Mathias
Thomas K. Hedemann
David K. Ludwig
AXINN, VELTROP & HARKRIDER LLP
90 State House Square
Hartford, Connecticut 6103
(860) 275-8100
mbecker@axinn.com
clandmon@axinn.com
tmathias@axinn.com
thedemann@axinn.com
dludwig@axinn.com
Christopher M. Gallo
950 F St NW
Washington, DC 20004
(202) 721-5413
cgallo@axinn.com
Attorneys for Appellee
January 9, 2019
62
Pernix Ireland Pain DAC v. Alvogen Malta Operations Ltd., 2018-2361
CERTIFICATE OF SERVICE
I, Simone Cintron, being duly sworn according to law and being over the age
of 18, upon my oath depose and say that:
Counsel Press was retained by AXINN VELTROP HARKRIDER, LLP, counsel
for Appellee to print this document. I am an employee of Counsel Press.
On January 9, 2019, counsel has authorized me to electronically file the
foregoing Brief for Appellee Alvogen Malta Operations Ltd. with the Clerk of
Court using the CM/ECF System, which will serve via e-mail notice of such filing
to all counsel registered as CM/ECF users, including the following principal
counsel for the other parties:
Dominick A. Conde
Venable LLP
1290 Avenue of the Americas, 19th Floor
New York, NY 10104
212-218-2204
dconde@venable.com
Principal Counsel for Appellants
Upon request from the Court of the e-filed document, six paper copies will
January 9, 2019 /s/ Simone Cintron

Counsel Press
63
CERTIFICATE OF COMPLIANCE WITH TYPE-VOLUME

LIMITATION, TYPEFACE REQUIREMENTS AND TYPE STYLE
REQUIREMENTS
1. This brief complies with the type-volume limitation of Federal Rule of Appellate
Procedure 32(a)(7)(B) or Federal Rule of Appellate Procedure 28.1(e)
X The brief contains 13,912 words, excluding the parts of the brief
exempted by Federal Rule of Appellate Procedure 32(a)(7)(B)(iii),or
The brief uses a monospaced typeface and contains lines of

text, excluding the parts of the brief exempted by Federal Rule of
Appellate Procedure 32(a)(7)(B)(iii).
2. This brief complies with the typeface requirements of Federal Rule of Appellate
Procedure 32(a)(5) or Federal Rule of Appellate Procedure 28.1(e) and the type
style requirements of Federal Rule of Appellate Procedure 32(a)(6)
X The brief has been prepared in a proportionally spaced typeface using

MS Word 2013 in a14 point Times New Roman font or
The brief has been prepared in a monospaced typeface using

in a ___ characters per inch_________ font.
January 9, 2019 /s/ Chad A. Landmon

Chad A. Landmon
Counsel for Defendant-Appellee
64

Alvogen Response Brief

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Alvogen Response Brief

Hochgeladen von

Copyright:

Verfügbare Formate

Case: 18-2361 Document: 31 Page: 1 Filed: 01/09/2019

PERNIX IRELAND PAIN DAC, PERNIX THERAPEUTICS, LLC,

Appeal from the United States District Court

BRIEF FOR APPELLEE

Matthew J. Becker Christopher M. Gallo

Attorneys for Appellee Alvogen Malta Operations Ltd.

1. The full name of every party or amicus represented by me is:

Alvogen Malta Operations Ltd.

2. The name of the real party in interest represented by me is:

Alvogen Malta Operations Ltd.

Alvogen Lux Holdings S.a.r.l; Alvogen Pharma Ltd.

Axinn, Veltrop & Harkrider LLP: Ryan D. Hersh, Seth I. Heller

decision in the pending appeal.

Dated: January 9, 2019 /s/ Chad A. Landmon

STATEMENT OF RELATED CASES .....................................................................1

STATEMENT OF THE ISSUES...............................................................................3

STATEMENT OF THE CASE ..................................................................................4

A. Prior Art Hydrocodone Formulations ...................................................4

SUMMARY OF ARGUMENT .................................................................................8

I. The District Court Correctly Held

to Combine and Reasonable Expectation of Success..........................13

2. Pernix Misrepresents the Standard for Reasonable

The District Court Correctly Applied

II. The District Court Correctly Held That the

B. The District Court Correctly

The Specifications Do Not Disclose

2. Alcon Concerns Different Types of Claims

3. Union Oil Is Inapposite. ............................................................60

Alcon Research Ltd. v. Barr Labs., Inc.,

Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,

Cooper Cameron Corp. v. Kvaerner Oilfield Prods., Inc.,

Endo Pharm. Inc. v. Teva Pharm. USA, Inc.,

Funk v. Stryker Corp.,

Gentry Gallery, Inc. v. Berkline Corp.,

Hybritech Inc. v. Monoclonal Antibodies, Inc.,

In Re: Copaxone Consol. Cases,

Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino,

Perricone v. Medicis Pharm. Corp.,

Pfizer, Inc. v. Apotex, Inc.,

Polaroid Corp. v. Eastman Kodak Co.,

Sanofi v. Watson Labs., Inc.,

Senju Pharm. Co. v. Lupin Ltd.,

Stratoflex, Inc. v. Aeroquip Corp.,

Tyco Healthcare Grp. LP v. Mut. Pharm. Co.,

Union Oil Co. of Cal. v. Atlantic Richfield Co.,

Univ. of Rochester v. G.D. Searle & Co.,

Vas-Cath Inc. v. Mahurkar,

Fed. R. Evid. 201(b)(2) ............................................................................................16

Fed. R. Evid. 201(c)(1) ............................................................................................16

Fed. R. Evid. 201(d) .................................................................................................16

Pernix Pernix Ireland Pain DAC and Pernix Therapeutics, LLC

Alvogen Alvogen Malta Operations Ltd.

760 patent U.S. Patent No. 9,265,760

499 patent U.S. Patent No. 9,339,499

Asserted Patents 760 patent and 499 patent

Claims 1-4, 11, 12, 17 and 760 patent and claim 1

POSA Person of ordinary skill in the art

PPA Patient-prescriber agreement

FDA Guidance for Industry: Pharmacokinetics in Patients

FDA Drug Safety Communication: Prescription

Devane U.S. Patent Application Publication No. 2006/0240105 A1

Jain U.S. Patent Application Publication No. 2010/0010030 A1

Area under the curve of the plasma concentration of an active

Maximum concentration observed in the blood following