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Jumping Through the
Shifting

Hoops of Biosimilarity:

A Primer for U.S. and South Korean Companies
©


By Lawrence A. Kogan, Esq.



Track 12
-

Biotech Patenting & Licensing:


Strategic Response in New Legal Environment and New Market


Session 2
-

Regulatory Approval on Biosimilars



Presented at


BIO
Korea 2011



Conference and Exhibition


Seoul, Korea


September 30, 2011



Abridged Version

9/30/11

ITSSD

2

Jumping Through the
Shifting

Hoops of Biosimilarity:

A Primer for U.S. and South Korean Companies
©

TABLE OF CONTENTS


I.
Economic

Profile

of

the

Biologics/

Biosimilars

Industry


II.
Intro

to

Biologics

Price

Competition

and

Innovation

Act

of

2009

(‘BPCIA’)

III.
Overview

of

the

BPCIA’s

Provisions


IV.
BPCIA’s

Implications

for

Patent

Licensing

V.
Key

Hatch
-
Waxman

Act

IP

Provisions


VI.
High

Profile

Post
-
Enactment

Interpretational/Implementation

Debates

About

Reference

Product

Exclusivity

VII.
BPCIA’s

Impact

on

International

Trade

VIII.
Conclusion



9/30/11

ITSSD

3

I. Economic Profile of the Biologics/ Biosimilars Industry


A.

Macro Data


Biotech

product

sales

(
100

world

drugs)

to

increase

from

33
%

in

2010

to

45
%

by

2016


U
.
S
.

share

of

world

biosimilar

market



72
.
2
%

(
2013
),

82
.
9
%
(
2014
)
;

Europe

share

of

world

biosimilar

market



76
.
3
%

(
2012
),

26
.
4
%

(
2013
),

16
.
3
%

(
2014
)


South

Korea

IP

and

data

exclusivity

laws

will

tighten,

inhibiting

new

product

opportunities

for

generics

producers
.

Crowded

domestic

market,

growing

pricing

&

cost

pressures,

drives

South

Korean

companies

to

produce

super
-
generics

and

biosimilars

(follow
-
on

biologics



‘FOBs’)


“[T]he

[Korean]

biosimilar

industry

depends

on

the

U
.
S
.

market

in

which

many

popular

biotechnology

drugs

...

will

see

their

patents

expire

between

2012

and

2019
.



“‘The

U
.
S
.

market

won’t

be

easy

for

Korean

firms

to

penetrate
...


B.
Micro

Data


$
1
.
2

billion+

development

cost

for

innovator

biologic

product

+

$
450

million

to

build

specialized

manufacturing

facilities


In

US,

8

to

10

years

for

biosimilar

development,

at

cost

of

$
100
-
$
200

million


Several

studies

show

biosimilar

cost

discount

to

biological

reference

product

will

be

no

more

than

10
%
-
30
%

due

to

smaller

#

of

FOB

market

entrants

C.
Anecdotal

Data/Prediction


US

&

European

biotech

drug

sales

not

in

line

with

prior

chemical

drug

sales


Dendreon

(Provenge

),

Seattle

Genetics

(Adcetris

),

Human

Genome

Sciences

(Benlysta

),

Bristol

Myers

Squibb

(Yervoy

),

Genentech/Roche

(Zelboraf

),

and

Centocor

Ortho

Biotech/Johnson

&

Johnson

(Zytiga)


High

cost/lack

of

automatic

substitution

between

FOB

&

pioneer

biologic

drugs

will

slow

FOB

market

penetration

and

revenues


9/30/11

ITSSD

4

II. Intro to Biologics Price Competition and Innovation Act of 2009 (‘BPCIA’)

A.


General Issues for Consideration


Signed

into

law

3
/
23
/
10
,

as

part

of

Patient

Protection

and

Affordable

Care

Act

of

2009

(PPACA)
;

amends

Sec
.

351

of

Public

Health

Services

Act

(PHSA)


Creates

an

abbreviated

approval

pathway

for

generic

‘biological

products’

that

are

demonstrated

to

be

highly

similar

(i
.
e
.
,

biosimilar)

to

or

interchangeable

with

an

FDA
-
licensed

reference

biological

product


Since

enactment,

USFDA

has

worked

to

establish

complete

and

final

guidance

on

such

pathway



many

difficulties

&

unanswered

questions

remain

due

to

the

relative

complexity

of

biologics

compared

to

chemically

based

drugs


USFDA

officials

have

looked

to

Europe

for

ideas
;

some

suggest

promulgating

rules

that

significantly

resemble

European

Medicines

Agency

(EMA)

biosimilar

guidelines


USFDA

has

no

simple

way

to

answer

the

critical

question

of

how

similar

a

biosimilar

must

be

to

the

branded

product

B.


Brief Overview of EU Biosimilars Pathway


Directive 2004/27/EC, amending Directive 2001/83/EC


Article 10.4


European Medicines Agency (EMA) biosimilar guidelines


Authorization

-

Application

submitted

to

secure

authorization

for

a

product

claimed

to

be

‘similar’

to

another

biological

medicine



the

‘reference

product’
.


The

licensing

route

for

biosimilars

is

based

on

the

principle

that
:

biologics

are

not

chemical

drugs

-

biologics

similar

to

a

reference

product

“do

not

usually

meet

all

the

conditions

to

be

considered

as

a

generic”


EMEA/CHMP/
42832
/
2005
;

EMEA/CHMP/BWP/
49348
/
2005
,

etc
.







9/30/11

ITSSD

5

II. Intro to Biologics Price Competition and Innovation Act of 2009 (‘BPCIA’)

B.
Brief Overview of EU Biosimilars Pathway (cont’d)


Data Exclusivity

-

‘8+2+1’


8

years

-

Biosimilar

application

first

accepted

only

after

8

years

from

initial

‘reference’

product

authorization


2

years

-

Once

biosimilar

application

is

accepted,

market

authorization

of

biosimilar

must

wait

another

2

years



i
.
e
.
,

placement

in

market

NOT

permitted

until

after

10

years

total

following

initial

‘reference’

product

authorization

(‘
8
+
2
’)



1

year

-

If,

during

the

first

8

years

of

data

exclusivity

reference

product

sponsor

obtains

an

authorization

for

new

therapeutic

indication(s)

which

bring(s)

‘significant

clinical

benefit’

in

comparison

with

existing

therapies,

data

exclusivity

extended

1

year

=

11

years

total

(‘
8
+
2
+
1
’)




9/30/11

ITSSD

6

III. Overview of the BPCIA’s Provisions


A
.


Biosimilarity

and

Other

Information


42

USC

262
(a)

&

(k)
;

Public

Health

Service

Act

(PHSA),

Sect
.

351
(a)&(k)



‘Biosimilar’

Product

-

“a

biological

product

that

is

the

subject

of

an

application

under

subsection

(k)

which

“is

‘highly

similar’

to

the

‘reference

product’

notwithstanding

minor

differences

in

clinically

inactive

components”

and

with

respect

to

which

“there

are

no

clinically

meaningful

differences

between

the

biological

product

and

the

reference

product

in

terms

of

the

safety,

purity,

and

potency

of

the

product”



‘Biological’

Product

-

“any

virus,

therapeutic

serum,

toxin,

antitoxin,

vaccine,

blood,

blood

component

or

derivative,

allergenic

product,

protein

(except

any

chemically

synthesized

polypeptide)

or

analogous

product,

or

arsphenamine

or

derivative

of

arsphenamine

(or

any

other

trivalent

organic

arsenic

compound),

applicable

to

the

prevention,

treatment,

or

cure

of

a

disease

or

condition

of

human

beings”


‘Reference’

Product

-

the

single

biological

product

licensed

under

subsection

(a)

against

which

a

biological

product

application

submitted

under

subsection

(k)

is

evaluated



USFDA

two
-
step

approach

to

reviewing

claim

of

‘biosimilarity’
:


First

-

Will

review

“analytic

data

showing

how

similar

[company]

compounds

are

to

an

FDA
-
approved

innovator

version


Second



Will

“determine

on

a

case
-
by
-
case

basis

how

much

animal

and

clinical

data

are

required

for

approval
.


9/30/11

ITSSD

7

III. Overview of the BPCIA’s Provisions


Also,

a

biosimilar

application

must

show

that
:


“Biological

product

and

reference

product

use

the

same

mechanism(s)

of

action

for

the

condition(s)

of

use

prescribed,

recommended,

or

suggested

in

the

proposed

labeling,

but

only

to

the

extent

the

mechanism(s)

of

action

are

known

for

the

reference

product
;



“The

condition(s)

of

use

prescribed,

recommended,

or

suggested

in

the

labeling

proposed

for

the

biological

product

were

previously

licensed

for

the

reference

product”
;



“The

route

of

administration,

dosage

form,

and

strength

are

the

same

for

the

biological

product

and

the

reference

product”
;

and



“The

facility

in

which

the

biological

product

is

manufactured,

processed,

packed,

or

held

meets

standards

designed

to

assure

that

the

biological

product

continues

to

be

safe,

pure,

and

potent
.


B.


Interchangeability


Once

‘Biosimilarity’

is

determined

can

seek

‘Interchangeability’

determination


Must

show

that

the

proposed

biological

product

“can

be

expected

to

produce

the

same

clinical

result

as

the

reference

product

in

any

given

patient”


Where

a

proposed

“biological

product

is

administered

more

than

once

to

an

individual”
:


Must

demonstrate

that

“the

risk

in

terms

of

safety

or

diminished

efficacy

of

alternating

or

switching

between

the

use

of

the

biological

product

and

the

reference

product

is

not

greater

than

the

risk

associated

with

using

the

reference

product

without

such

alteration

or

switch”


An

Interchangeability

determine

permits

presciption

of

biosimilar

by

pharmacy
;

NO

approval

of

physician

required

9/30/11

ITSSD

8

III. Overview of the BPCIA’s Provisions

C.


Exclusivity


BPCIA

provides

for

both

marketing

exclusivities

and

data

protection

for

brand
-
name

biological

reference

products


‘Marketing

Exclusivity’

-

an

FDA
-
administered

proprietary

right

that

prevents

others

from

filing

an

application

for

approval

of

a

follow
-
on

product


Blocks

competitors

wishing

to

develop

their

own

clinical

data

in

support

of

marketing

approval

application


‘Data

Protection’

-

prevents

competitors

from

relying

upon

clinical

data

developed

by

the

brand
-
name

firm

in

support

of

FDA

approval

of

a

competing

version

of

the

product


Does

NOT

block

competitors

wishing

to

develop

their

own

clinical

data

in

support

of

marketing

approval

application


i
.


General

Exclusivity



4

years

-

NO

acceptance

of

FOB

‘biosimilarity’

or

‘interchangeability’

application

until

4

years

after

‘reference’

product

authorization/license

[**European

Union



8

years]


12

years



NO

approval

of

‘biosimilarity’

or

‘interchangeability’

application

until

12

years

after

date

of

‘reference’

product

authorization/license

(
+

8

years
)

[**European

Union

+

2

years]


BPCIA



12

years

total

exclusivity

-

NO

market

entry

(without

extension)


EU

EMA



10

years

total

exclusivity

-

NO

market

entry

(without

extension)


MARKETING

EXCLUSIVITY

or

DATA

EXCLUSIVITY??

9/30/11

ITSSD

9

III. Overview of the BPCIA’s Provisions


‘Reference

Product’

Exclusivity

Coverage

Unavailable
:


NO

‘reference’

product

4
year/
12
year

exclusivity

coverage

for

a

subsequent

application

(made

by

reference

product

sponsor,

manufacturer,

licensor,

predecessor

in

interest,

or

other

related

entity)

for
:


“a

change

(
not

including

a

modification

to

the

structure

of

the

biological

product)

that

results

in

a

new

indication,

route

of

administration,

dosing

schedule,

dosage

form,

delivery

system,

delivery

device,

or

strength”

or


“a

modification

to

the

structure

of

the

biological

product

that

does

not

result

in

a

change

in

safety,

purity,

or

potency
.



YES

‘Reference

Product’

4

year/
12

year

exclusivity

coverage

for

a

subsequent

application

will

be

extended

to
:


“a

modification

to

the

structure

of

the

biological

product

resulting

in

a

change

in

safety,

purity,

or

potency”



essentially

a

new

biological

product

deserving

of

its

own

license



‘Orphan’

Drug

Exclusivity



If

‘reference

product’

is

designated

for

a

rare

disease

or

condition



Exclusivity

Period

=

the

later

of
:


NO

approval

of

biosimilar

or

interchangeable

application

relating

to

such

disease

or

condition

for

7

years

from

reference

product

authorization/license

(if

reference

product

first

licensed

under

Section

526

of

the

Federal

Food,

Drug,

and

Cosmetic

Act

-

Pre
-
BPCIA

license)

or


NO

approval

of

biosimilar

or

interchangeable

application

relating

to

such

disease

or

condition

for

12

years

from

reference

product

authorization/license

(if

reference

product

licensed

under

Section

351

of

PHSA

-

post
-
BPCIA

license)


**

Because

of

BPCIA

enactment,

if

‘reference’

product

first

licensed

under

FFDCA

has

used

up

all

or

some

of

its

7

years

of

exclusivity,

it

can

receive

up

to

5
+

years

extra

exclusivity

but

no

more

than

12

years

in

total

exclusivity


9/30/11

ITSSD

10

III. Overview of the BPCIA’s Provisions


‘Pediatric Studies’ Exclusivity


‘Reference

Product’

4

year/
12

year

exclusivity

coverage

will

be

extended

6

months

to

4
.
5

years

/
12
.
5

years

if
:


USFDA

determines

that

information

relating

to

use

of

‘reference

product’

will

produce

health

benefits

in

pediatric

population
;


USFDA

makes

a

written

request

for

pediatric

studies
;



Reference

product

sponsor

agrees

to

such

request
;



Such

studies

are

timely

completed

using

appropriate

formulations

for

each

age

group

for

which

the

study

is

requested
;

and


Reports

of

such

studies

are

submitted

and

accepted

by

USFDA



ii. ‘Interchangeability’ Exclusivity


1 year


Protects 1
st

successful biosimilar applicant



NO

FDA ‘interchangeability’ determination/approval for 2
nd

‘biosimilar’ applicant
until
earlier

of:


1 year

after 1st commercial marketing of the 1st interchangeable biosimilar
or


18

months

after

a

final

court

decision

on

all

patents

in

[a

patent

infringement]

instituted

under

BPCIA

procedure

against

the

1
st

interchangeable

biosimilar

applicant

or

dismissal

of

such

action

(with

or

without

prejudice)

or


42

months

after

approval/licensure

of

1
st

first

interchangeable

biosimilar

product

where

such

product’s

applicant

has

been

sued

under

under

BPCIA

procedure

and

such

litigation

is

still

ongoing

within

such

42
-
month

period

or


18

months

after

approval/licensure

of

1
st

interchangeable

biosimilar,

if

such

applicant

was

not

sued



9/30/11

ITSSD

11

III. Overview of the BPCIA’s Provisions

D.
Patent Protection


BPCIA

defines

an

‘act

of

patent

infringement’

as

also

including
:


the

submission

of

a

biosimilar

application

with

respect

to

a

patent

included

in

the

reference

product

sponsor’s

initial

and

supplementary

patent

lists

compiled

pursuant

to

the

BPCIA’s

patent

dispute

procedure

AND


the

submission

of

a

biosimilar

application

with

respect

to

a

patent

that

the

reference

product

sponsor

could

reasonably

assert

would

be

infringed

by

the

commercialization

or

importation

of

the

applied
-
for

biosimilar

product,

even

though

the

biosimilar

applicant

failed

to

comply

with

its

statutory

obligation

to

provide

a

copy

of

the

biosimilar

application

to

the

reference

product

sponsor


The

BPCIA

creates

a

new

extensive

mandatory

statutory

patent

dispute

procedure
:


to

resolve

potential

patent

disputes

(i
.
e
.
,

issues

of

patent

validity/infringement)

between

a

brand

name

biologic

drug

(‘reference

product’)

sponsor

and

a

biosimilar

applicant

before

an

FDA
-
approved

biosimilar

product

is

commercially

marketed



This

procedure

is

triggered

by

the

USFDA’s

acceptance

for

review

of

a

submitted

biosimilar

application


BPCIA’s

patent

dispute

procedure

consists

of

three

stages
:


Pre
-
litigation

information

exchange


Early

stage

litigation


Late

stage

litigation


BPCIA’s

dispute

procedure

is

intended

to

reduce

patent

litigation

through

long

cooling
-
off

period
;

however

whether

this

objective

will

be

met

is

highly

questionable

9/30/11

ITSSD

12

III. Overview of the BPCIA’s Provisions


i.

Pre
-
Litigation Information Exchange (Takes place over 6 month period)


Biosimilar

Applicant

provides

‘information’

-

confidentially

to

reference

product

sponsor

within

20

days

of

USFDA

notifying

it

received

biosimilar

application,

including
:


A

copy

of

the

biosimilar

application
;



Information

describing

the

process

of

manufacture

of

proposed

biological

product
;


Additional

information

reference

product

sponsor

or

representative

requests
;

and


Other

information

biosimilar

applicant

deems

relevant

&

appropriate



‘Information’

shall

be

given

to
:


Reference

product

sponsor
;


Reference

product

sponsor’s

‘outside’

counsel
;

and


Reference

product

sponsor’s

‘inside’

counsel
;


‘Information

may

be

given

to
:


The

owner

of

a

patent

exclusively

licensed

to

the

reference

product

sponsor,

if

the

owner

retains

a

right

to

assert

the

patent

or

participate

in

litigation



Reference

Product

Sponsor

provides

‘information’



to

biosimilar

applicant,

no

later

than

60

days

after

receiving

biosimilar

application,

including
:


A

list

of

reference

product

patents

‘believed’

to

be

infringed

if

biosimilar

product

would

be

used,

sold

or

imported

into

the

US
;

and


Specific

patents

on

such

list

that

the

reference

product

sponsor

would

be

prepared

to

license



9/30/11

ITSSD

13

III. Overview of the BPCIA’s Provisions


Biosimilar

Applicant

responds

to

reference

product

sponsor

not

later

than

60

days

after

receipt

by
:


Responding

to

each

identified

patent

on

reference

product

sponsor’s

list
;

or


Providing

own

list

of

reference

product

sponsor

patents

against

which

it

believes

a

claim

of

patent

infringement

could

reasonably

be

asserted


At

a

minimum,

must

submit

a

detailed

statement

substantiating,

claim

by

claim,

its

position

concerning

why

the

patent

is

invalid

or

unenforceable,

or

will

not

be

infringed


Reference

Product

Sponsor

responds

to

biosimilar

applicant

no

later

than

60

days

by
:


Providing,

with

respect

to

each

patent

reference

product

sponsor

has

listed,

a

detailed

statement

substantiating,

claim

by

claim,

its

own

position

why

each

listed

patent

is

valid

and

enforceable

and

will

be

infringed

if

biosimilar

product

is

commercialized



ii
.

Early

Patent

Litigation

Negotiations/Information

Exchange

(
45

day

process

if

agree)


Both

Parties

have

15

days

from

reference

product

sponsor’s

last

information

dispatch

to

negotiate

in

good

faith

which

patents

to

litigate


If

Agreement

is

reached,

reference

product

sponsor

commences

a

patent

infringement

action

not

later

than

thirty

(
30
)

days

from

the

date

of

such

agreement,

based

on

the

agreed

upon

list

of

patents
;



Reference

Product

Sponsor

must

effectively

litigate

2
x

patents

listed

by

biosimilar

applicant

(can’t

decline

to

litigate

designated

patents

or

else

may

lose

rights)


Biosimilar

applicant

must

notify

FDA

within

thirty

(
30
)

days

of

receiving

complaint


If

NO

Agreement

is

reached,

biosimilar

applicant

must

notify

the

reference

product

sponsor

of

the

number

of

patents

it

believes

should

be

litigated
.



Within

five

(
5
)

days

of

such

notice,

BOTH

PARTIES

simultaneously

exchange

their

respective

lists

of

specifically

identified

patents

which

each

party

seeks

to

litigate


Reference

Product

Sponsor’s

list

cannot

exceed

#

of

patents

on

biosimilar

applicant’s

list


Thus,

biosimilar

applicant’s

patent

list

effectively

controls

total

#

of

patents

to

be

litigated

9/30/11

ITSSD

14

III. Overview of the BPCIA’s Provisions


iii
.

Late

Stage

Patent

Litigation/Pre
-
Commercialization


The

BPCIA

patent

dispute

procedure

makes

available

to

the

Parties

the

following

judicial

remedies,

with

conditions
:


Preliminary

Injunctions


Declaratory

Judgments


Permanent

Injunctions


Preliminary

Injunctions

(PRI)


Reference

Product

Sponsor

may

seek

a

PRI

after

receiving

the

biosimilar

applicant’s

180
-
day

advance

notice

of

biosimilar

product’s

1
st

commercialization,

but

before

the

actual

commercial

marketing

occurs

(during

this

180

day/
6

month

window)


Reference

Product

Sponsor

may

use

a

PI

to

add

to

the

list

of

patents

for

litigation,

any

patents

it

has

acquired

or

exclusively

licensed

(‘subsequently

acquired/licensed

patents’)

since

it

first

exchanged

patent

lists,

against

which

it

could

reasonably

assert

a

claim

of

patent

infringement,

if
:

»
Timely

notified

-

within

thirty

(
30
)

days

of

execution

of

acquisition/licensing

agreement



(if

not

timely

notified,

such

patents

CANNOT

be

asserted

by

Reference

Product

Sponsor

in

subsequent

infringement

litigation)


PRI

is

effective

until

a

court

determines

patent

validity,

infringement

or

enforcement


PRI

applies

to

patents

of

both

parties

on

pre
-
litigation

initial

patent

lists

that

could

reasonably

be

asserted

as

having

been

infringed,

but

were

not

included

in

the

early

stage

patent

suit

(if

patent

not

on

initial

list,

cannot

obtain

PRI

with

respect

to

it)

9/30/11

ITSSD

15

III. Overview of the BPCIA’s Provisions



Declaratory

Judgments

(DJ)


DJs

are

NOT

available

to

either

Party,

when

biosimilar

applicant

has

timely

provided

a

copy

of

the

biosimilar

application

&

other

information

to

the

reference

product

sponsor,

UNTIL

AFTER

reference

product

sponsor

receives

biosimilar

applicant’s

180
-
day

advance

commercialization

notice


The

DJ

may

seek

a

determination

of

infringement,

validity

or

enforceability

with

respect

to

(i
.
e
.
,

DJ

applies

to
:
)

any

patents

included

in

either

the

initial

patent

list

or

a

supplementary

patent

list

of

subsequently

acquired

or

licensed

patents


Reference

Product

Sponsor

may

seek

a

DJ

where

the

biosimilar

applicant

failed
:

»
To

timely

provide

the

reference

product

sponsor

with

any

of

the

required

information
;

or


»
To

timely

fulfill

its

obligations

to

the

reference

product

sponsor

or

to

the

FDA

Secretary

under

these

patent

dispute

proceedings
:

»
To

timely

exchange

patent

lists

»
To

timely

notify

USFDA

of

its

receipt

of

RPS’

complaint

»
To

timely

respond

to

RPS’

supplementary

list

of

subsequently

licensed

patents

»
To

notify

RPS

prior

to

biosimilar

product’s

1
st

commercial

marketing




Biosimilar

applicant

may

seek

DJ

after

it

files

180

day

notice

of

commercialization

in

an

effort

to

control

litigation



Permanent

Injunctions

(PMI)


Reference

Product

Sponsor

may

seek

and

court

may

grant

PMI

after

the

biosimilar

applicant

product’s

1
st

commercialization

but

before

the

reference

product

sponsor’s

patent

expires



A

PMI

can

only

follow

a

final,

non
-
appealable

court

decision

of

infringement

obtained

in

an

‘Immediate

Action

for

Patent

Infringement’

initiated

under

the

BPCIA’s

dispute

procedure

9/30/11

ITSSD

16

IV. BPCIA’s Implications for Patent Licensing

A.
BPCIA

Patent

Dispute

Resolution

Process

Will

Feature

Patents

Not

Included

in

FDA

Orange

Book)

Portending

More

Extensive

Litigation


BPCIA

does

not

exclude

process

patents

from

the

patent

dispute

procedure


But

FDA

Orange

Book’s

exclusion

of

process

patents

renders

‘prior

art’

searches

more

difficult,

and

patent

litigation

more

likely

for

biosimilar

applicants


FDA

Orange

Book

contains

a

list

of

all

approved

products,

including

their

composition

&

method

patents

B
.

Patent

Owners

May

Be

Included

in

Reference

Product

Sponsor

Litigation

Without

Prior

Notice


BPCIA’s

patent

dispute

procedure

permits,

but

does

NOT

require,

a

biosimilar

applicant

to

provide

certain

information

directly

to

the

owner

of

a

patent

exclusively

licensed

to

the

reference

product

sponsor

with

respect

to

the

reference

product


BPCIA’s

patent

dispute

procedure

requires

a

biosimilar

applicant

to

provide

confidential

information

to

a

reference

product

sponsor

and

its

‘inside’

&

‘outside’

counsel,

but

does

not

require

any

of

them

(
indirectly)

to

share

such

information

with

third
-
party

owners

of

patents

exclusively

licensed

to

the

reference

product

sponsor


BPCIA’s

patent

dispute

procedure

requires

a

reference

product

sponsor

to

include

in

its

follow
-
up

lists

to

the

biosimilar

applicant

subsequently

acquired

or

exclusively

licensed

patents

within

30

days

of

the

exclusive

licensing

agreement’s

execution,

but

does

not

ensure

that

the

patent

owner

will

be

apprised

of

such

submission

or

of

any

subsequent

patent

litigation


BPCIA’s

patent

dispute

procedure

does

not

require

patentees

to

participate

in

the

confidential

disclosure

process,

which

could

encourage

their

nonparticipation

9/30/11

ITSSD

17

IV. BPCIA’s Implications for Patent Licensing

C.
Reference

Product

Sponsor’s

Failures

May

Trigger

Forfeiture

of

Patent

Rights


i
.

Denial

of

Preliminary

Injunction

to

Reference

Product

Sponsor




May

result

from

reference

product

sponsor’s

failure

to

include

a

patent

on

the

initial

pre
-
litigation

patent

list

it

previously

provided

to

the

biosimilar

applicant



ii
.

Denial

of

Preliminary

Injunction

to

Reference

Product

Sponsor




Only

a

‘reasonable

royalty’

can

be

awarded

by

a

court

in

a

successful

reference

product

sponsor

patent

infringement

action

against

a

biosimilars

applicant,

if

a

reference

product

sponsor

failed
:


To

timely

commence

such

action

(within

the

prescribed

30

days

where

both

parties

agree

on

patents

to

be

litigated)

with

respect

to

a

patent

identified

in

the

reference

product

sponsor’s

pre
-
litigation

or

early

litigation

patent

list

provided

to

the

biosimilar

applicant
;

or


To

prosecute

an

otherwise

timely

filed

patent

infringement

action

to

judgment

in

good

faith

(i
.
e
.
,

it

sought

dismissal

of

the

action)


iii
.

Denial

of

‘Standing’

to

Patent

Owner

to

Bring

Patent

Infringement

Action



A

reference

product

sponsor’s

failure

to

include

an

exclusively

licensed

patent

on

an

initial

or

supplementary

patent

list

provided

to

the

biosimilar

applicant

pursuant

to

the

BPCIA

dispute

procedure

will

preclude

the

owner

of

such

patent

from

bringing

a

patent

infringement

action

with

respect

to

potentially

infringing

biosimilar

product


9/30/11

ITSSD

18

IV. BPCIA’s Implications for Patent Licensing

D.

Proactive Measures for Counsels to Consider



Must

carefully

review

clients’

license

agreements

to

evaluate

the

likelihood

that

an

exclusively

licensed

patent

will

fall

subject

to

a

dispute

involving

a

biosimilar

product


Undertake

cost
-
benefit

of

securing

exclusive

vs
.

non
-
exclusive

license

in

light

of

litigation

risk


Exclusive

licensor

(patent

owner)

should

ensure

that

its

licensee

provides

prompt

notice

of

a

biosimilar

legal

challenge


Exclusive

licensor

(patent

owner)

should

ensure

that

it

retains

for

itself

the

right

to

play

an

active

role

in

the

reference

product

sponsor’s
:


Biosimilar

application

review
;


Decision

to

include

or

not

include

the

licensed

patent

on

its

patent

list(s)
;

and



Prosecution

of

an

infringement

action

involving

the

licensed

patent


Reference

product

sponsor
-
exclusive

licensee

should

restrict

the

exclusive

licensor’s

(patent

owner’s)

role

in

the

patent

dispute

procedure
:


To

reduce

the

risk

of

procedural

delay
;


To

retain

discretion

over

whether

to

assert

exclusively

licensed

patents


To

control

the

prosecution

of

patent

litigation

and

settlement


Determine

how

inclusive

the

list

of

patents

to

be

litigated

should

be

for

purposes

of

defining

the

initial

scope

of

litigation


Weigh

whether

statements

of

facts

and

law

concerning

listed

patents

should

be

intentionally

obtuse

given

evidentiary

value

of

statements

in

litigation


9/30/11

ITSSD

19

V. Key Hatch
-
Waxman Act IP Provisions

A.
Exclusivity

-

The

Hatch
-
Waxman

Act

established

several

different

types

of

marketing

exclusivities
:



i. New Chemical Entities


5 years from approval of NDA for a particular active ingredient (moiety)


NO reliance
on data; NO generic application accepted


ii. New Clinical Studies


3

years

from

approval

for

NDA

or

supplemental

NDA

if

reports

of

new

studies

essential

to

FDA

application


iii. Orphan Drug


7 years for specific indication


iv. Pediatric Studies


6 months


B.
Patent Protection


i. Statutory Exemption from Patent Infringement Claims


To make, use or sell patented invention solely for uses relating to FDA marketing
approval


Generic mfrs can commence work on a generic version of an approved drug at any time
during the life of the patent so long as the work furthers compliance with FDA regs

9/30/11

ITSSD

20

V. Key Hatch
-
Waxman Act IP Provisions


ii. Patent Term Extension


For lost time during regulatory review, provided patentee exercises due diligence


Not to exceed 5 years


Full remaining patent term not to exceed 14 years


iii. Challenging Approved Drug Patents/Dispute Settlement


Generic

applicant

that

files

certification

stating

that

FDA

Orange

Book
-
listed

patent

for

approved

originator

drug

is

invalid

or

will

not

be

infringed

(“a

paragraph

IV

certification”)

MUST

NOTIFY

patent

owner,

who

may

bring

infringement

suit

with

45

days

of

receipt

of

such

notice


Automatic

Stay

of

generic

application

if

patent

owner

or

original

drug

applicant

timely

files

infringement

action


iv. Rewards for Challenging Approved Drug Patents (FDA Orange Book
-
listed)


180 day exclusivity for FIRST generic to file “paragraph IV certification”


9/30/11

ITSSD

21

VI
.

High

Profile

Post
-
Enactment

Interpretational/Implementation

Debates

About


Reference

Product

Exclusivity

A.
USFDA

Federal

Register

Notice

Description

of

Marketing

Exclusivity

and

Solicitation

of

Public

Advice

(
10
/
5
/
10
)

B.
Congressional

Research

Service

(CRS)

Report

Discusses

Distinction

Between

Market

Exclusivity

and

Data

Protection

With

Respect

to

What

Type

of

Exclusivity

the

BPCIA

Provides

(
10
/
26
/
10
)


Market

Exclusivity

&

Data

Protection/Exclusivity

C.
Letter

From

3

Principal

US

House

of

Representatives

/BCPIA

Authors

to

USFDA

Discussing

The

Character

&

Period

of

Exclusivity

(
12
/
10
/
10
)


Data

Exclusivity,

NOT

Market

Exclusivity

D.
Letters

From

BIO

and

PhRMA

to

USFDA

Discussing

Character,

Period

and

Extensions

of

Exclusivity

to

Supplementary

Applications,

‘Related

Entities’

and

Third
-
Party

Transferees

(
12
/
23
/
10
)


No

market

authorization

until

after

patent

&

all

exclusivities

expire


Non
-
qualifying

supplemental

filings

of

reference

product

sponsor

AND

reference

product

affiliated

entities

are

entitled

to

the

remaining

exclusivity

periods

relating

to

the

reference

product

-

‘Evergreening’



“UMBRELLA”

EXCLUSIVITY

E.
Letter

From

5

US

Senators

to

USFDA

Discussing

Distinction

Between

Marketing

Exclusivity

and

Data

Protection

With

Respect

to

What

Type

of

Exclusivity

BPCIA

Provides

(
1
/
7
/
11
)


Data

Exclusivity

NOT

Marketing

Exclusivity


NO

Separate

12

year

Data

Exclusivity

for

same

product

or

for

product

structurally

modified

without

a

change

in

safety,

purity

or

potency

9/30/11

ITSSD

22

VI
.

High

Profile

Post
-
Enactment

Interpretational/Implementation

Debates

About

Reference

Product

Exclusivity

F.
Letter

From

Generic

Pharmaceutical

Manufacturers,

Healthcare

Service

Providers,

etc
.

to

USDFA

Discussing

Character

of

Period

of

Exclusivities

BPCIA

Provides

(
1
/
20
/
11
)


Concurrent

4

year/

8

year

periods



4

years



Data

Exclusivity

&

Marketing

Exclusivity


8

years



Marketing

Exclusivity



Data

of

reference

product

can

be

relied

on

G.
Letter

From

4

Senators

to

USFDA

Expressing

Their

Opposition

to

BPCIA’s

12
-
year

Exclusivity

Period

(
1
/
24
/
11
)


FDA

can

begin

reviewing

biosimilar

applications

during

12

years

exclusivity

period

H.
President Obama’s Line
-
By
-
Line 2012 Budget Review Proposing a Reduction to
the BPCIA Exclusivity Period For Reference Products


From 12
-
years to 7 years,
and the Denial of ANY Additional Exclusivity Period, to Reduce National
Healthcare Costs (2/15/11)


NO Evergreening


Saves $2.34 billion in US healthcare costs

9/30/11

ITSSD

23

VII. BPCIA’s Impact on International Trade

A.
The

Korea
-
US

Free

Trade

Agreement

(KORUS

FTA)


Brief

Chronology

of

the

Signing

and

Amending

of

the

Treaty

(
2007
)


April

2007

negotiations

concluded


June

2007

FTA

signed


Brief

Discussion

of

the

‘May

10

Agreement’

and

USTR

‘Side

Letter’

(
2007
)


Implementation

of

FTA

Marketing/

Data

Exclusivity

&

‘Patent

Linkage’

provisions

delayed

for

18

months


Inclusion

of

WTO

TRIPS

Doha

Declaration

provisions/’flexibilities’

due

to

pressure

of

110
th

Congress

&

health

activist

groups

-

(e
.
g
.
,

compulsory

licensing

for

benefit

of

developing

countries)



Brief

Discussion

of

Obama

Administration’s

Renegotiation

of

the

Treaty

(
2009
-
2010
)


December

2010



Agreed

to

extend

implementation

of

FTA

Marketing/Data

Exclusivity

&

Patent

Linkage

provisions

an

additional

18

months

(now

a

total

of

36

months)


Environmental

and

labor

provisions

added

to

FTA


Discussion

of

Signing

&

Ratifying

of

EU
-
South

Korea

FTA

(
2010
-
2011
)


5

years

Data

Exclusivity


European

Commission

signed

Oct
.

2010


European

Parliament

ratified

Feb
.

2011


EU
-
South

Korea

FTA

in

effect

in

July

2011


Creates

added

pressure

for

US

to

ratify

KORUS
-
FTA



competitive

disadvantage

9/30/11

ITSSD

24

VII. BPCIA’s Impact on International Trade


Discussion

of

Data

Exclusivity

&

Patent

Linkage

Provisions

of

Final

Text

of

Renegotiated

KORUS
-
FTA


Article

18
.
9
.
1
(a)

-

5

years

Data

Exclusivity



NO

reliance

on

original

drug

approval

or

data

for

5

years

in

Korea


Article

18
.
9
.
1
(b)



NO

reliance

on

original

drug

approval

or

data

of

prior

marketing

approvals

of

original

drug

in

another

country

for

5

years


Article

18
.
9
.
2



3

years

exclusivity

in

Korea

or

in

another

country

for

new

clinical

information

essential

to

the

FDA

regulator’s

approval

of

a

pharmaceutical

product


Article

18
.
9
.
4



Prevents

Korean

regulators

from

terminating

data

protection

period

with

the

expiration

of

a

patent


Article

18
.
9
.
5



Patent

Linkage



Korea

must

implement

measures

in

its

marketing

approval

process

to

prevent

generic

drug

approval

during

the

term

of

the

originator’s

drug

patent

AND

must

disclose

identity

of

generic

applicants

seeking

marketing

approval

during

the

patent

term


Articles

18
.
9
.
3
/

18
.
11



WTO

Doha

Declaration

on

TRIPS

Agreement

on

Public

Health

provisions

ensuring

availability

of

‘compulsory

licenses’

to

meet

‘public

interest’

health

needs


Patent

Linkage



Korean

regulators

must

investigate

and

confirm

that

a

generic

drug

applicant

seeking

marketing

approval

does

NOT

infringe

an

existing

patent



if

a

patent

claim

exists,

the

regulator

must

deny

marketing

approval

until

the

patent

term

expires



Discussion

of

Ongoing

US

Ratification

Delays

(
2010
-
2011
)


9/30/11

ITSSD

25

VII. BPCIA’s Impact on International Trade

B.
The

Trans
-
Pacific

Partnership

Agreement

(TPPA)



4

Nations

(Brunei,

Chile,

NZ,

Singapore)

signed

in

2005
;

Took

effect

in

Nov
.

2006


Discussion

of

Original

TPPA

&

Obama

Administration’s

Pursuit

of

Expansive

TPPA

Negotiations,

Focusing

on

Data

Exclusivity

and

Patent

Linkage

Provisions

(
12
/
2009
)


Notification

to

US

Congress

in

Fed

Register

Notice

seeking

public

comment



US

to

push

for

a

truly

Asia

regional

agreement

to

set

benchmarks


9

countries

now

negotiating

(
5

new

countries,

besides

US)



Australia,

Malaysia,

Peru,

Vietnam


Letter

From

18

House

of

Representatives

Committee

on

the

Judiciary

Members

to

President

Obama

Expressing

the

Need

to

Pursue

the

Highest

Level

American

IP

Protections

in

TPPA

Negotiations

Using

the

Korea

FTA

as

a

Starting

Point

(KORUS
-
plus)

(
2
/
4
/
11
)


Discussion

of

Leaked

TPPA

Position

Papers

of

New

Zealand

Government

&

US

Industry,

and

US

Government

Draft

TPPA

Text

(
12
/
4
/
10
;

12
/
13
/
10
;

2
/
10
/
11
)


Public

Citizen

NGO

leak

showing

New

Zealand

support

for

‘TRIPS
-
aligned’

position

opposing

US

‘TRIPS
-
plus’

position


KEI

NGO

leak

showing

US

position

to

use

KORUS
-
FTA

as

baseline

for

TPPA


KEI

NGO

leak

showing

US

proposed

IP

chapter

leaving

open

provisions

for

marketing/data

exclusivity

&

patent

linkage


Discussion

About

How

USTR’s

Announcement

that

it

Would

Table

its

Complete

TPPA

IP

Proposal

for

Negotiation

by

Mid
-
June

2011

to

Speed

Up

Talks,

Triggered

Heated

Public

Debate

in

the

US

About

Which

Negotiating

Position

USTR

Should

Pursue

-

‘May

10
-
KORUS’

or

‘KORUS
-
plus’

(April

2011
)


One

pharma

executive

quoted

as

saying

‘KORUS
-
plus’

with

12

year

Marketing/Data

Exclusivity

for

Biologics

integrating

BPCIA

is

needed

as

baseline

with

China

and

Asia

region

9/30/11

ITSSD

26

VII. BPCIA’s Impact on International Trade


Letter

From

14

Democratic

House

Ways

&

Means

Committee

Members

to

USTR

Kirk

Seeking

for

USTR

to

‘Defend’

‘KORUS
-
May

10


as

the

US

position

in

the

TPPA

Negotiations

(
7
/
26
/
11
)


Letter

From

40

Pro
-
Free

Trade

House

Members

to

President

Obama

Urging

TPPA

IP

Chapter

to

Include

12

Years

Marketing/Data

Exclusivity

Protection

for

New

Biologic

Drugs

(
7
/
27
/
11
)


Letter

From

10

Democratic

House

of

Representative

Members

to

USTR

Kirk

Urging

that

‘May

10
-
KORUS

be

the

Starting

Point

for

US

TPPA

Negotiating

Position

and

that

Any

Data

Exclusivity

Provisions

to

be

Included

Should

be

Voluntary

(
8
/
2
/
11
)


Letter

From

7

Democratic

House

of

Representative

Members

to

President

Obama

Recommending

that

US

Refrain

From

Negotiating

Any

TPPA

IP

Provisions

Related

to

Exclusivity

for

Biosimilars

Medicines

(
8
/
4
/
11
)


BPCIA

still

too

without

full

understanding

of

its

impact,

to

call

for

12

years

Exclusivity


Urging

Adherence

to

Presidential

Call

for

7

Years

Marketing/Data

Exclusivity


Letters

From

Group

of

37

US

Senators

and

2

US

House

of

Representatives

Members

From

Colorado

to

President

Obama

Calling

For

USTR

To

Secure

12

Years

of

Marketing/Data

Exclusivity

Rather

Than

President’s

Line
-
by
-
Line

Review

of

2012

Budget

Plan

Recommending

7

Years,

and

Rather

Than

5

Years

Marketing/Data

Exclusivity

of

KORUS
-
FTA’s

“May

10

Agreement”

(
9
/
12
/
11
)

9/30/11

ITSSD

27

VIII. Tentative Conclusions


The BPCIA:


Is

unquestionably

a

formidable

and

ambitious

piece

of

legislation

that

aims

to

promote

scientific

innovation

and

safe

and

cost
-
effective

access

to

healthcare

.



Recognizes

that

biologic

drugs

and

biosimilar

products

are

far

more

technically

complex

and

economically

costly

and

time
-
consuming

to

develop

and

market

than

conventional

pharmaceuticals

and

their

generic

counterparts,

and

that

the

scientific

challenges

and

associated

risks

regulators

face

when

evaluating

the

biosimilar

features

of

live

biologic

proteins

are

far

greater

than

those

faced

when

assessing

the

bioequivalence

of

chemically

synthesized

molecules
.



Provides

a

delicate,

if

not

tenuous,

balance

between

the

rights

and

interests

of

patent

owners,

biosimilar

applicants

and

the

public

at

large,

that

can

potentially

result

in

a

diversion

of

scarce

economic,

intellectual

and

social

capital

away

from

critical

product

development

efforts

and

towards

ill
-
conceived

and

unproductive

IP
-
based

litigation

at

administrative

and

judicial

fora

that

could

severely

delay

the

introduction

of

badly

needed

medicines
.


Compels

US

FDA

officials

to

look

toward

Europe’s

longer

experience

with

establishing

a

biosimilars

pathway,

and

South

Korean

and

other

APEC

member

nation

FDA

authorities

to

compare

their

emerging

biosimilar

pathways

with

those

of

Europe

and

the

US

to

ensure

lessons

learned

and

to

facilitate

greater

harmonization
.



Reflects

a

shifting

multipolar

dynamic,

that

will

likely

need

to

be

updated

over

time

to

keep

pace

with

new

biotechnology

discoveries

and

evolving

manufacturing

and

processing

techniques,

as

well

as,

emerging

life

science

business

models
.


Has

arguably

already

triggered

domestic

and

cross
-
border

R&D,

manufacturing

and

distribution

realignments
.

9/30/11

ITSSD

28

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