First to File and Beyond:
Paragraph IV Business Strategies
THOMSON REUTERS INTELLECTUAL PROPERTY & SCIENCE
GENERICS & API INTELLIGENCE
Benjamin Burck
Research Analyst and Project Manager
Generics & API Intelligence
benjamin.burck@thomsonreuters.com
Generics & API Intelligence at Thomson Reuters
• 20 years of expertise in global generics
• Unique research that tracks global generic API development
and manufacturing activities
• Intelligence appears in Newport Premium™ database for:
– Strategy, Planning and Product Targeting
– Business Development & Licensing
– Competitive & Business Intelligence
– API Sourcing
– Patents & Intellectual Property
• Supports Life Sciences consulting projects
• Serves 300 customers operating in 43 countries
• Team based in Portland, Maine
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Agenda
• Hatch-Waxman Basics
• Paragraph IV Strategies
• Market Realities
• Anticipating Competitors
• Examples
3
Orange Book Patent Listing
• 21 USC §355(b)(1)
The applicant shall file with the application (NDA)
the patent number and the expiration date of any
patent which claims the drug for which the
applicant submitted the application or which claims
a method of using such drug and with respect to
which a claim of patent infringement could
reasonably be asserted if a person not licensed by
the owner engaged in the manufacture, use, or
sale of the drug.
4
Orange Book Patent Listing
• Patents that must be listed
– Active ingredient (drug substance)
– Formulation or composition (drug product)
– Method of approved use
• Patents that may not be listed
– Processes
– Packaging
– Intermediates
5
ANDA Patent Certification
• 21 USC §355(j)(2)(A)(vii)
[An ANDA shall contain] a certification, in the opinion of the
applicant and to the best of his knowledge, with respect to
each patent which claims the listed drug… or which claims a
use for such listed drug for which the applicant is seeking
approval
(I)
that such patent information has not been filed,
(II) that such patent has expired,
(III) of the date on which such patent will expire, or
(IV) that such patent is invalid or will not be infringed by
the manufacture, use, or sale of the new drug for
which the application is submitted
6
Incentives and Protections
• 180-day market exclusivity
– First applicant to submit a substantially complete ANDA
(first-to-file)
– May be shared by multiple applicants
– Subject to forfeiture
• 30-month stay of FDA approval
– If patent owner or NDA holder sues the ANDA applicant
for patent infringement within 45 days of receiving notice
of the Paragraph IV certification
– Runs from date of notification or expiration of NCE
exclusivity
– May be lengthened or shortened by the court
7
ANDA Submission
• New Chemical Entity (NCE) Exclusivity
– Five year data exclusivity from the date of first NDA
approval for products containing chemical entities never
previously approved by FDA
– ANDAs with Paragraph IV certification may be submitted
four years after regulatory approval (NCE -1), but may not
receive approval until the expiration of the exclusivity
period
• Other Exclusivities
– ANDAs may be submitted at any time, with or without
Paragraph IV certification
– ANDAs may not receive approval until the expiration of
the exclusivity period
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“Lawsuits such as these are an ordinary and
expected part of the process of obtaining approval
to commercialize a generic drug product in the
United States.”
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First-Time Generic Approvals 2007-2011
Source: Newport Premium™
10
Possible Generic Paragraph IV Strategies
Targets
Market Position
• Everything
• First filer
• Blockbusters
• Subsequent filer
• Niche Products
– Limited competition
– Highly competitive market
– Formulation
– Therapeutic Class
– Limited API
– Limited Sales
• Line Extension
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Generic Strategies
•
We plan to continue to expand our Global Division through targeted ANDAs and a first-to-file and firstto-market strategy. Our products and product candidates are generally difficult to formulate and
manufacture, providing certain barriers to entry for potential competitors.
(Impax Laboratories, Form 10-K)
•
The “Niche Generics” program is targeted on developing those generic drug products that are:
–
Difficult to develop for technical reasons, especially injectable and ophthalmic dosage forms
–
No or very limited API source (InnoPharma, Company Website)
•
We believe that we can maximize the profitability of our generic product opportunities by continuing our
proven track record of bringing to market high quality products that are difficult to formulate or
manufacture, or for which the API is difficult to obtain. (Mylan, Form 10-K)
•
The strategy in the Rx Pharmaceuticals segment is to be the first to market with those new products
that are exposed to less competition because they have more difficult to develop formulations and cost
much more to complete. (Perrigo, Form 10-K)
•
We constantly seek to expand our range of generic products, with an emphasis on high-value products,
including those with high barriers to entry. (Teva, Form 20-F)
•
Our strategy in the U.S. is to develop generic pharmaceuticals that are difficult to formulate or
manufacture or will complement or broaden our existing product lines. (Watson, Form 10-K)
•
Differentiation is one of the rudiments that success thrives on and the company strategically selects
difficult to develop, high technology products and niche markets to get ANDA approvals.
(Wockhardt, Annual Report 2011)
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Paragraph IV Reality
• Any product may be a generic target
• More companies are pursuing a Paragraph IV
strategy
• Challenges to complex products are increasing
• Competition and specialization in the generic
industry has led to products with $20 million or less
in sales being considered opportunities
• Products may be targeted even before NDA
approval
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Gralise (gabapentin)
First FDA Approval
January 28, 2011
U.S. Product Launch
October 10, 2011
First ANDA Submission
October 31, 2011
NDA Holder
Depomed
US Sales
$ 0.5M
(October – December 2011)
Orange Book Patents
Known ANDA Filers
(Source: Depomed )
Patent No
Expiration
6,340,475
September 19, 2016
6,488,962
June 20, 2020
6,635,280
September 19, 2016
6,723,340
October 25, 2021
7,731,989
October 25, 2022
7,438,927
February 26, 2024
Actavis, Incepta, Watson
Source: Newport Premium™
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First Paragraph IV Patent Certifications
Posted by FDA
Source: Newport Premium™
15
Corporate Groups Associated with
Paragraph IV Patent Certifications
Source: Newport Premium™
16
Top Paragraph IV Filers by Group
Source: Newport Premium™
17
Market Reality
• Price erodes with each generic entrant
• Price erosion continues as the generic market
matures
• Aggressive individual players can greatly affect the
price for all
• First filer’s market share advantage persists after
additional generic entry
• Authorized generics are to be expected
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Known ANDA Filers per Challenged Product
Source: Newport Premium™
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First Filers
• Settlement leverage
• Limited competition at launch
• Higher initial price
• “First Mover” market share
• Marketing message
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NCE-1 Opportunities
Source: Newport Premium™
21
2008 NCE -1 Products
Trade Name
Active Ingredient
Dose Form
# of Known
P IV ANDAs
Sensipar
cinacalcet hydrochloride
Tablet
1
Enablex
darifenacin hydrobromide
Extended-release tablet
3
Lovaza
omega-3 acid ethyl esters
Capsule
3
Cymbalta
duloxetine hydrochloride
Delayed-release capsule
9
Tarceva
erlotinib hydrochloride
Tablet
2
Lunesta
eszopiclone
Tablet
10
Fosrenol
lanthanum carbonate hydrate
Chewable tablet
4
Alimta
pemetrexed disodium
Injectable
4
Lyrica
pregabalin
Capsule
10
Source: Newport Premium™
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Subsequent Filers
• Travel a worn path
– Lower litigation costs
– Known legal arguments
– Settlement precedent
• More informed decisions
• Authorized generic deal?
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Lunesta (eszopiclone)
First FDA Approval
December 15, 2004
NCE Exclusivity
December 15, 2009
First ANDA Submission
December 15, 2008
NDA Holder
Sepracor (now Sunovion)
US Sales
$ 774.5M
(12 months ending September 30, 2011)
Orange Book Patents
(Source: IMS Health)
Patent No
Expiration
6,319,926
January 16, 2012
7,381,724
January 16, 2012
6,864,257
August 30, 2012
6,444,673
February 14, 2014
Known ANDA Filers
Dr. Reddy's, Glenmark, Lupin, Mylan, Orchid, Roxane, Sun,
Teva, Watson, Wockhardt
Generic Launch per Settlement
November 30, 2013
Source: Newport Premium™
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Lunesta (eszopiclone): Mylan
Paragraph IV Notification
March 10, 2009 (Alphapharm)
DMF
Manufacturer
Submission Date
Matrix Laboratories
March 25, 2008
Related Patents
Newport First Associated Date
Primary Patent
Patent Type
Priority Date
WO-2006136866
Process
June 21, 2005
WO-2007232537
Formulation
April 26, 2006
WO-2007124025
Process
April 12, 2007
June 21, 2005
Source: Newport Premium™
25
Lunesta (eszopiclone): Teva
Paragraph IV Notification
February 9, 2009
DMF
Manufacturer
Submission Date
TAPI Puerto Rico
November 14, 2008
Related Patents
Newport First Associated Date
Primary Patent
Patent Type
Priority Date
WO-2007109799
Product (derivative)
March 23, 2006
WO-2007124025
Process
April 20, 2006
WO-2008094690
Process
April 20, 2006
WO-2008002629
Process
June 26, 2006
WO-2009002552
Formulation
June 25, 2007
March 23, 2006
Source: Newport Premium™
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Lunesta (eszopiclone): Some Others Involved
Dr. Reddy’s Laboratories
Farmak
Glenmark
Sun Pharmaceutical Industries
Patent
September 5, 2005
API Commercially Available in Newport
March 9, 2007
DMF Submitted
September 13, 2008
Patent (Czech Republic)
August 11, 2000
API Commercially Available in Newport
January 18, 2006
DMF Submitted
March 7, 2008
Patent
January 17, 2006
Unconfirmed API Activity in Newport
January 30, 2006
DMF Submitted
August 4, 2008
API Commercially Available in Newport
September 5, 2008
DMF Submitted
November 29, 2008
Other Market Launches
February 28, 2007 (India)
Source: Newport Premium™
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Bystolic (nebivolol HCl)
First FDA Approval
December 17, 2007
NCE Exclusivity
December 17, 2012
First ANDA Submission
December 19, 2011
NDA Holder
Forest Laboratories
US Sales
$ 341.1M
(12 months ending September 30, 2011)
Orange Book Patents
Known ANDA Filers
(Source: IMS Health)
Patent No
Expiration
5,759,580
June 2, 2015
6,545,040
December 17, 2021
Alkem, Amerigen, Glenmark, Hetero, Indchemie, Torrent, and
Watson
Source: Newport Premium™
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180-Day Exclusivity Forfeiture
Generic exclusivity is forfeited for failure to market
upon the later of:
The earlier of:
–
75 days after approval of the first
applicant’s ANDA
–
30 months after the date of ANDA
submission
75 days after any of the
following with respect to
any applicant with tentative
approval:
–
Court decision that the patent is
invalid or not infringed (no further
appeal)
–
Settlement order or consent
decree with judgment of invalidity
or noninfringement
–
Patent listing is withdrawn
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Integrilin (eptifibatide)
First FDA Approval
December 15, 2004
First ANDA Submission
September 30, 2008
NDA Holder
Schering (Merck)
ANDA Filer
Teva
Orange Book Patents
Patent No
Expiration
5,686,570
November 11, 2014
5,747,447
May 5, 2015
5,756,451
November 11, 2014
5,807,825
September 15, 2015
5,5968,902
June 2, 2015
Generic Launch per Settlement
June 2, 2015
Source: Newport Premium™
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Kaletra (lopinavir/ritonavir)
First FDA Approval
October 28, 2005
First ANDA Submission
December 23, 2008
NDA Holder
Abbott
ANDA Filer
Mylan
Orange Book Patents
Patent No
Expiration (including PED exclusivity)
5,541,206
Jan 30, 2014
5,648,497
Jan 15, 2015
5,886,036
May 19, 2014
5,914,332
Jun 13, 2016
6,037,157
Dec 26, 2016
6,284,767
Aug 15, 2016
6,703,403
Dec 26, 2016
7,148,359
Jan 19, 2020
7,364,752
May 10, 2021
8,025,899
Mar 26, 2028
Case status
Stayed until July 1, 2014
Source: Newport Premium™
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Thank You!
Benjamin Burck
Research Analyst and Project Manager
Thomson Reuters
+1 207 871 9700 x35
benjamin.burck@thomsonreuters.com
thomsonreuters.com
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