This document discusses strategies for expanding branded generic drug businesses into Latin America. It provides an overview of a conference on branded generics in emerging markets, including panel discussions on intellectual property issues in Mexico and Brazil. Key opportunities for branded generics in Latin America are identified, as well as risks associated with bringing patented products to the region. Clinical trial strategies and intellectual property landscapes in various Latin American countries are also examined.

1. Business, IP, and Clinical
Strategies for Expansion into
Latin America with Branded
Generics
BRANDED GENERICS: NEW AVENUE FOR
RX EXPANSION INTO EMERGING
MARKETS
FEBRUARY 27-28, 2012
HUB CIRA CENTER IN PHILADELPHIA, PA
DAISY RIVERA-MUZZIO, R.PH, MS, MBA
PRESIDENT
ACUMEN BIOPHARMA, LLC

2. Panel Members
Elias Rios Navarro- Ana Claudio Mamede-
Intellectual Property - Intellectual Property -
Arochi, Marroquin& Danneman Siemsen, Biger
Lindner - Mexico & Ipanema Moreira - Brazil
Woody Bryan - Business
Janet Mora-Regulatory &
Development - Supernus
Marketing – Link Pharma
Pharmaceuticals
Daisy Rivera-Muzzio -
Business Development &
Intellectual Property -
Acumen BioPharma

3. What is a branded generic in the US?
3
Off Patent Intellectual
Regulatory
drug molecule property
Formulation /
New Dosage form Manufacturing Process NDA- 505 (b) (2)
Components
Differentiated drug
delivery system Clinical studies to
New Indication(s) support label
information
New Product Strength
Technology
3-5 years market
New combination of exclusivity
API’s Method of Use
A novel invention February 27-28, 2012

4. Require clinical studies
Differences
Not necessarily bioequivalent to the innovator
between
Branded vs. Distribution channels- Requires commercial promotional strategies
Commoditized
Generics Premium Price
More expensive development
It is NOT an Proprietary technology
Authorized Generic
May have market exclusivity 3-5 years
February 27-28, 2012

5. ¡ Value added or Branded generics
Branded also exists in the rest of the world,
generics: different regulations applied and a
Rest of the real benefit to the patient must be
world proven to get premium price
approval in those countries with
drug product price regulations
¡ A generic product can be
commercialized under a brand or
trade name following retail
promotion strategies similar to
those of innovator products.
Examples: Greece, France, Spain,
Eastern EU, Latin America
February 27-28, 2012

6. FDA and UK’s
National “Prescription products that are
either
Health
Services
( NHS) 1) novel dosage forms of off-patent
products produced by a
Definition of
manufacturer that is not the
Branded
originator of the molecule,
Generics
or
2) a molecule copy of an off-patent
product with a trade name”.
February 27-28, 2012

7. Examples of Branded Generics- US
Intermezzo offers Tirosint is the first The NitroMist Suprenza is the first
a new dosage form, and only T4 therapy Aerosol Delivery and only orally
new strengths and in a liquid gel cap System disintegrating tablet
new indication for formulation Unique aerosol (ODT) phentermine
off patent molecule- delivery system that formulation.
(middle of the night maintains the
awakening) potency and stability
of nitroglycerin for
up to 36 months (or
approximately 230
sprays)
February 27-28, 2012

8. Generic Evolution
8
— “The generics makers that will grow most are
those that focus on higher-tech formulations
and specialty drugs, rather than the easily
commoditized tablets and capsules common in
primary care. The trend is shifting towards less
competitive, yet commercially attractive
segments such as difficult-to-produce generics,
specialty generics and biosimilars.”
Frost & Sullivan
February 27-28, 2012

9. Global Growth - 2003-2012E(%)
9
Source: EMC managers, BSCH, BBVA, JPM, DB February 27-28, 2012

10. Latin America, Pharmaceutical Market
10
$11.4 bn
2008 $7.8 bn
sales
$28.8 bn
Expected growth >70% in
$4.0 bn
Resistors to growth:
Growth Opportunities
5 years:
• Compulsory Licensing ( Brazil)
• Launch of new products, • Intellectual property Annulment
• Increased out of pocket ( Venezuela)
spending • Prohibition of use of second patents
• Public demand for quality
pharmaceuticals
Characteristics of generic drug
Steady population growth
policy in Latin America:
$3.0 bn
Resistors to growth
of 1%, and a balanced sex • Lack of separate generic approval protocol
ratio • Absence of a link between patent and
regulatory agencies impedes the flow of
10 % of the population is knowledge regarding the authorization of
over 60 years old infringing products;
• Lack of sufficient data exclusivity enables
Non-communicable generic players to access clinical data for
diseases especially development of generics;
neuropsychological and • Bioequivalence is not a mandatory
CVS disorders cause more requirement for generic approval in many
Latin American countries
casualties in LA than • Drug pricing Regulated by Government
communicable diseases February 27-28, 2012
agencies

11. Country-wise sales Forecasts, 2008-2014
Latin America Pharmaceutical Market Outlook to 2014- Business insight
11 February 27-28, 2012

12. Forecast Sizes of Latin American Markets
Latin America Pharmaceutical Market Outlook to 2014- Business insight
12 February 27-28, 2012

13. SWOT - Latin American Regulatory Landscape
Latin America
Pharmaceutical
Market Outlook
to 2014-
Business insight
13 February 27-28, 2012

14. Clinical Trials in Latin America
Latin America Pharmaceutical Market Outlook to 2014- Business insight
14 February 27-28, 2012

15. PhRMA Special 301 submission regarding Latin
America, 2009
Latin America
Pharmaceutical
Market Outlook
to 2014-
Business insight
15

16. Panel Discussion
16
— Discovering opportunities in the Latin American
markets for branded generics drugs
— Comparing IP and patent compliance in Latin
America vs. the United States
— Filling the gaps in the approval process for
clinical trial initiated in Latin America
Daisy Rivera- Janet Mora Woody Ana Claudia Elias Rios
Muzzio Brian Mamede Navarro
Carneiro
Acumen BioPharma Link Pharma Supernus Dannemann-Siemsen, Arochi,
Bigler & Ipanema Marroquin&
Moderator Regulatory & Business Moreira Lindner
Marketing Development Intellectual Property- Intellectual
Brazil Property-
Mexico

17. • W H AT I S T H E M A R K E T
O P P O R T U N I T Y FO R B R A N D E D
G E N E R I C S I N L AT I N A M E R I CA ?
• W H A T A R E T H E R I S K S A S S O C I A T E D
WITH BRINGING A PATENTED
PROTECTED PRODUCT IN LATIN
AMERICA
• W H A T A R E T H E S T R A T E G I E S T O H A V E
A SUCCESSFUL COMMERCIALIZATION
OF THESE PRODUCTS IN LA?
•
February 27-28, 2012

18. Intellectual
Property
Assessment
for
Branded
Generics
in
Mexico
Elias
Rios
Navarro
erios@aml.com.mx

19. Mexico.-­‐
Marke5ng
Authoriza5on
API
Linkage
Special
forms
API
Patent
Secondary
Pharm
Linkage
by
Expired
Patent
Composi@on
li@ga@on
Process
No
linkage
Civil
Courts
Nullity Trial / Const. Action Sales
Cancelled
IP infringement
Marke@ng
Before MX PTO
Damages
Authoriza@on
PTO
Preliminary
No
nullity
Lost
Profits
Granted
to
Bond
Sales
Measures
Decision
Infringement
40%>
+
No
patent
Fine
holder
Counter
claim
No
nullity
Counterbond
No
Infringement
Execu@on
of
the
In
force
bond
Nullity
No
Infringement

20. BRANDED
GENERICS:
New
Avenue
for
Rx
Expansion
Into
Emerging
Markets
February
27-­‐28,
2012
Hub
Cira
Center
in
Philadelphia,
PA
Intellectual
Property
Issues
Ana
Claudia
Mamede
Carneiro
dannemann.com.br
©
2012
D012
Dannemann
Siemsen.
Aights
reserved.
©
2 annemann
Siemsen.
All
r ll
rigths
reserved.
20

21. BRAZIL
-­‐
Prosecu@on
of
patent
cases
§ Steps:
§ Request
for
examina5on:
3
years
from
filing
date
§ Third
par5es
may
file
a
pre-­‐grant
opposi5on
§ If
allowed
by
PTO,
for
pharmaceu5cal
cases,
the
applica5on
will
be
sent
to
ANVISA
(Sanitary
Agency)
for
prior
consent:
• If
ANVISA
allows,
the
case
will
return
to
PTO
(final
fees)
• If
ANVISA
rejects,
…
§ If
rejected
by
PTO,
an
appeal
is
applied
• If
the
PTO
allows,
the
case
will
be
sent
to
ANVISA
for
prior
consent
• If
the
PTO
rejects,
the
administra5ve
instance
will
be
ended
§ Third
par5es
may
file
a
post-­‐grant
opposi5on
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
21

22. BRAZIL
-­‐
Prosecu@on
of
patent
cases
§ Backlog
of
8-­‐10
years
for
the
publica5on
of
a
first
technical
opinion
§ No
difference
between
the
different
technical
fields
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
22

23. BRAZIL
-­‐
Prosecu@on
of
patent
cases
q Patent
Office
hired
approximately
350
new
examiners
q Faster
prosecu5on
expected
q Fast
track
q Poten5al
infringement
cases
(warning
le[er
to
the
alleged
infringer)
q Ar5cle
40
of
IP
law
–
Minimum
10
year
patent
term
as
of
grant
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
23

24. BRAZIL
-­‐
ANVISA’s
prior
consent
q Provisional
Measure
#
2006
of
Dec
14,
1999
q Law
#
10,196
of
Feb
14,
2001
q Art.
229-­‐C
of
the
IP
Law
9279/96
§ “grant
of
patents
to
pharmaceu5cals
products
and
processes
are
subject
to
prior
approval
by
ANVISA”
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
24

25. BRAZIL
-­‐
Prior
approval
(ANVISA)
q Since
2003
examining
substan5ve
patentability
criteria
q Grounds
for
non-­‐approval
q lack
of
novelty
and/or
inven5ve
step
q lack
of
enablement
q addi5on
of
new
ma[er
q second
use
=
discovery
q mandatory
restric5on
of
scope
of
Markush-­‐type
claims
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
25

26. BRAZIL
-­‐
Recent
Developments
(ANVISA)
q A[orney
General’s
Office
(AGU)
Opinions
(2011)
q Recent
decision
from
the
Federal
Court
of
Brasília
“The
men(oned
rule
[art.
229-­‐C]
is
uncons(tu(onal
since
it
wrongfully
revokes
ar(cle
4
quarter
of
the
Paris
Union
Conven(on,
lacking
reasonability,
and
also
duplicates
the
technical
examina(on
for
patentability
unnecessarily
and
unreasonably,
a
rule
that
is
both
internal
and
conven(onal
and
that
executes
a
cons(tu(onal
order
to
protect
patent
rights
as
a
fundamental
guarantee.”
(Astrazeneca
v.
ANVISA
and
BPTO
–
Court
Ac5on
n.29724-­‐20.2010.4.01.3400,
01.12.2011,
8th
Federal
Court)
dannemann.com.br
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2012
Dannemann
Siemsen.
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rigths
reserved.
26

27. ANVISA’s recent publications
DOU 04.07.2011 DOU 07.10.2011 DOU 07.11.2011
Total 23 41 8
Approval 13 41 8
Straight 13 35 2
After rebuttal 0 3* 0
After compliance of office
0 1 2
action
After appeal 0 2 4
Rejection 10 0 0
* 1) lack of enablement (Article 25 - IPL); 2) lack of inventive step (Article 13 - IPL); e 3) restriction to the content of the
examples (Articles 24 and 25 - IPL)
dannemann.com.br
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2012
Dannemann
Siemsen.
All
rigths
reserved.
27

28. BRAZIL
–
Non-­‐patentable
maders
§ Non-­‐patentable
§ Therapeu5c,
surgical
and
diagnos5c
methods
applied
to
human
or
animal
bodies
§ Living
beings
and
parts
thereof,
including
cells
even
if
modified
§ Naturally
occurring
biological
material,
even
if
isolated
• Microorganisms
• Extracts
and
substances
• DNA/RNA
sequences
§ Second
medical
use
(PTO
accepts,
but
ANVISA
does
not)
dannemann.com.br
©
2012
Dannemann
Siemsen.
All
rigths
reserved.
28

29. BRAZIL
-­‐
Access
to
Brazilian
biodiversity
§ Since
2000,
mandatory
authoriza5on
to
perform
R&D
in
and
to
manufacture
products
derived
from
plants
and
animals
of
the
Brazilian
biodiversity
§ Indica5on
of
source
of
gene5c
resource
and
access
authoriza5on
number
through
recent
PTO`s
office
ac5ons
based
on
Norma5ve
Acts
§ Relevant
fines
were
applied
on
companies
dannemann.com.br
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2012
Dannemann
Siemsen.
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rigths
reserved.
29

30.
Thank
you!
acmamede@dannemann.com.br
dannemann.com.br
©
2012
Dannemann
Siemsen.
All
rigths
reserved.
30

31. Janeth
Mora
LinkPharma
LLC
The
Cira
Hub
Center
Philadelphia,
February
27,
2012

32. Brazil
Mexico
Argen@na
Key
Regulatory
Requirements
(ANVISA)
(COFEPRIS)
(ANMAT)
Bioavailability
study
(if
changes
to
innovator)
If
approved
in
Reference
country
Bioequivalence
(with
reference
product)
If
approved
in
Reference
country
Good
Manufacturing
Prac@ces
Inspec@on
visit
Stability
in
Zone
IVB
Cer@ficate
of
Pharmaceu@cal
Product
(CPP)

33. Take away Points
33
— An effective due diligence to develop your own
branded generic strategy in Latin America should
consider :
¡ Local partnerships
¡ Collaborations with the government
¡ Understanding of markets unmet needs
¡ Innovative manufacturing technology to drive low cost
¡ Local partners are interested in manufacturing rights
¡ Regulatory Process is decentralized
¡ Prior FDA/ EMA approval could be leveraged
¡ Previous research of local patent standing
¡ Limit on royalties on technology transfers/ licensing
transactions
February 27-28, 2012

34. Thank you Gracias
Obrigada
FOR ADDITIONAL INFORMATION
DR.MUZZIO@ACUMENBIOPHARMA.COM
WWW.ACUMENBIOPHARMA.COM