Вы находитесь на странице: 1из 77

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
Case: 18-2361 Document: 31 Page: 2 Filed: 01/09/2019

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:

Alvogen Malta Operations Ltd.

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
Alvogen Malta Operations Ltd.

i
Case: 18-2361 Document: 31 Page: 3 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 4 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 5 Filed: 01/09/2019

2. Alcon Concerns Different Types of Claims


and Different Issues. .................................................................57

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


D. ................................60

CONCLUSION ........................................................................................................61

iv
Case: 18-2361 Document: 31 Page: 6 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 7 Filed: 01/09/2019

,
....................................................................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
Case: 18-2361 Document: 31 Page: 8 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 9 Filed: 01/09/2019

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

viii
Case: 18-2361 Document: 31 Page: 10 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 11 Filed: 01/09/2019

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%

760 patent claim 3) wherein the dosage unit provides a


PK Limitations 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 14%, 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 30%

760 patent claim 4) wherein the dosage unit provides a


release profile of hydrocodone that does not increase average
hydrocodone Cmax in subjects suffering from mild hepatic

x
Case: 18-2361 Document: 31 Page: 12 Filed: 01/09/2019

impairment relative to subjects not suffering from renal or


hepatic impairment in an amount of more than 9%, and the
release profile of hydrocodone 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%

760 patent claim 19) wherein the dosage unit provides a


release profile of hydrocodone that does not increase average
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

760 patent claim 12) wherein the dosage unit provides a


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%

760 patent claim 17) wherein the dosage unit provides a


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
Case: 18-2361 Document: 31 Page: 13 Filed: 01/09/2019

renal or hepatic impairment is in the range of about 300


ng*h/mL to about 500 ng*h/mL;
(2) the average hydrocodone AUC0-inf per 20 mg of
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;
(3) the average hydrocodone AUC0-inf per 20 mg of
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

499 patent claim 1) wherein the dosage unit provides a


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
Case: 18-2361 Document: 31 Page: 14 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 15 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 16 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 17 Filed: 01/09/2019

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

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
Case: 18-2361 Document: 31 Page: 19 Filed: 01/09/2019

(¶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
Case: 18-2361 Document: 31 Page: 20 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 21 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 22 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 23 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 24 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 25 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 26 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 27 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 28 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 29 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 30 Filed: 01/09/2019

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

(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
Case: 18-2361 Document: 31 Page: 32 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 33 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 34 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 35 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 36 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 37 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 38 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 39 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 40 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 41 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 42 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 43 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 44 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 45 Filed: 01/09/2019

(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
Case: 18-2361 Document: 31 Page: 46 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 47 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 48 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 49 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 50 Filed: 01/09/2019

, 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
Case: 18-2361 Document: 31 Page: 51 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 52 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 53 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 54 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 55 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 56 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 57 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 58 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 59 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 60 Filed: 01/09/2019

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).

The Specifications Do Not Disclose


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
Case: 18-2361 Document: 31 Page: 61 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 62 Filed: 01/09/2019

(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
Case: 18-2361 Document: 31 Page: 63 Filed: 01/09/2019

(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
Case: 18-2361 Document: 31 Page: 64 Filed: 01/09/2019

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

The Specifications Do Not Disclose


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
Case: 18-2361 Document: 31 Page: 65 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 66 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 67 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 68 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 69 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 70 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 71 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 72 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 73 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 74 Filed: 01/09/2019

(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
Case: 18-2361 Document: 31 Page: 75 Filed: 01/09/2019

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
AXINN, VELTROP & HARKRIDER LLP
950 F St NW
Washington, DC 20004
(202) 721-5413
cgallo@axinn.com
Attorneys for Appellee
Alvogen Malta Operations Ltd.

January 9, 2019

62
Case: 18-2361 Document: 31 Page: 76 Filed: 01/09/2019

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
Case: 18-2361 Document: 31 Page: 77 Filed: 01/09/2019

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
AXINN, VELTROP & HARKRIDER LLP
Counsel for Defendant-Appellee

64