Hatch-Waxman
As Amended (MMA)
Thomas O. Henteleff
Kleinfeld, Kaplan and Becker, LLP
November 9, 2005
Hatch-Waxman
2
Title I
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ANDAs
505(b)(2)
Exclusivity
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Patent
5-year – New Chemical Entity
3-year –
180-day
Other (orphan and pediatric)
3
Title II
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Infringement of Patent
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Bolar exemption (not an act of infringement)
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Solely for uses
Reasonably related to development and submission
Under Federal law which regulates drugs
An act of infringement to submit ANDA or
505(b)(2)
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Basis for Paragraph IV Litigation
Injunction as to effective date of application
No damages unless commercial marketing
4
Title II
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Patent Extension
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NCE
Up to 5 years
No more than 14 years
½ IND + NDA – lack due diligence
One per drug/per patent
5
Patent Exclusivity
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Patent Listing
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Requirements:
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A patent that claims a drug or method of use to which
a claim of patent infringement could reasonably be
asserted
Relates to 505(b)(1) and (b)(2)
Failure to timely list is basis for withdrawal and/or loss
of HW patent exclusivity
Improper listing subject to delisting and anti-trust
concerns
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Patent Listing
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Patents Covered
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Drug Substance (active ingredient)
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Subject to pending or approved
Same/polymorph
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Must certify test data showing perform the same
If listed, ANDA eligible
Drug Product (formulation and composition)
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Subject to pending or approved
Includes product by process
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Patent Listing

Patents Covered
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Method of Use
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Must identify section of pending or approved
labeling that corresponds
Indications, dosing regimens, use in
combination with other drugs- PK data
8
Patent Listing
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Patents Not Covered
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Process patents
Metabolites
Intermediates
Packaging
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Patent Listing – 314.53
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When to submit
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If issued at time 505(b)(1) or (b)(2) is submitted or
amended
 FDA Form 3542a
Update within 30 days of approval
 FDA Form 3542
 Orange Book listing/Public Display
If Supplement that relates to change in formulation,
indication, condition of use, route of administration,
strength or any change that relates to a drug, drug product
or method of use patent
Within 30 days after issues
Correction
10
ANDA


Prior to HW limited to generics of DESI-effective drugs (pre1962)
Approval based upon establishing bio-equivalence to a
reference listed drug (RLD) and CMC data

Generally, must be the same as RLD with respect to active(s)
and labeling, except:


Approved Suitability Petition-strength, dosage form, route of
administration, combination (21 CFR 314.93)
Labeling differences due to different manufacturer (e.g., name,
expiration dating), inactives or differencs resulting from
outstanding exclusivity that do not render the drug product less
safe or effective than the listed drug for any remaining nonprotected conditions of use (21 CFR 314.94, 314.127, and
314.150(b)(10))
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ANDA

Subject to patent and non-patent exclusivity

Once filed cannot amend or supplement to
refer to a different listed drug, except for new
strength
First to file a Paragraph IV potentially entitled
to a 180-day exclusivity

12
505(b)(2)
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Prior to HW “Paper NDA”
Relies in part on investigations which were not conducted by
or on behalf of the applicant and for which applicant has not
obtained a right of reference
Published literature (historical paper NDA)
Relies on agency’s findings of safety and effectiveness
of an approved listed drug
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If there is a listed drug which is pharmaceutically equivalent drug
to proposed it should be identified as the RLD?
Cannot be submitted if duplicate of listed and eligible for ANDA or
if only difference is bio-equivalence profile relating to extent or
unintentional rate
Examples: NCE (different salt), new indication, OTC switch,
strength, dosage form
13
505(b)(2)
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
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Subject to patent and non-patent
exclusivity (if rely on for safety and
effectiveness data)*
Potentially entitled to non-patent and
patent exclusivity
No 180-day exclusivity
* King Pharmaceutical vs. FDA (July 2004)
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Patent Certification/Statement

Paragraph I – Patent Information has not
been filed
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

No relevant patents
Application may be made effective immediately
Paragraph II – The listed patents have
expired

Application may be made effective immediately
15
Patent Certification/Statement
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Paragraph III – The date the listed patents expire
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
Application may be made effective on expiration date of
patent
Paragraph IV – The listed patent[s] are invalid, notinfringed or not enforceable

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
License Agreement
Application may be made effective immediately unless
within 45 days of receipt of notice infringement action
brought for a patent subject to certification and for which
patent information was filed before ANDA or (b)(2)
application (except amendments and supplements)
deemed substantially complete
Must provide certification for listed patent even if patent
could not result in 30 month stay (i.e., filed after ANDA or
(b)(2))
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Patent Certification/Statement

viii Statement – The listed method of use
patent does not claim the use for which the
applicant seeking approval (carve-out)

Limitation – Not permitted if renders generic less
safe or effective than listed drug for remaining
non-patented condition of use
17
Paragraph IV Notification
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Must notify patent owner (designated representative)
and holder of NDA for RLD
Must include detailed statement of factual and legal
basis
Must give notice within 20 days after FDA notifies
applicant that application has been filed
If an Amendment or Supplement must be given at time
filed
Based on MMA FDA revoked rule that notice not
required if applicant had already provided notice
Must amend application to certify notice has been sent
and provide for documented receipt (21 CFR 314.52,
314.95)
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30-Month Stay

Conditions

Patent listed before applicable ANDA or 505(b)(2)
filed (MMA)

MMA generally precludes multiple 30-month stays
because only applies with respect to patents filed prior
to ANDA or 505(b)(2)



New rule only applies to patents submitted after 8/13/03
Old rule if patent timely submitted ANDA would have to be
amended if sued triggered a new 30-month stay (FDA by
regulation tried to limit through notification)
Could be multiple 30-month stay under new rules if initially
IV and III and convert III into IV
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30-Month Stay
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Paragraph IV
Patent Owner on NDA holder sues within 45 days of
notice
Court may shorten or lengthen 30-month stay if
either party to action fails to reasonably cooperate in
expediting action
Court may issue an injunction against commercial
marketing until decides thereby effectively extending
the 30-month stay
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30-Month Stay
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When Terminated
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District Court decision that patent invalid, not
infringed or not enforceable (including any
substantive determination that no cause of action)
Date of Settlement or Consent degree that patent
invalid not infringed
Date of Court of Appeals decision reversing lower
court decision of infringement
21
30-Month Stay


If 30-month stay expires and no finding of
infringement ANDA/505(b)(2) may be made
effective upon the expiration
If Court finds infringement ANDA/505(b)(2)
cannot receive effective approval until
relevant patent expires
22
180-Day Exclusivity

First to submit a substantially complete ANDA with
Paragraph IV for listed patent

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May be separate exclusivities for separate patents or
shared exclusivity for filings on the same date
Doesn’t apply to 505(b)(2)
Prior to MMA (December 8, 2003) 180-day clock
triggered by earlier of commercial marketing or court
decision

Paragraph IV filed prior to 12/08/03 court decision still
triggers; however if court trigger occurs after 12/08/03 the
triggering court decision is the court from which no appeal
can be taken other than certiorari (Court of Appeals)
23
180-Day Exclusivity

Paragraph IV certification after MMA 180-day
clock triggered by commercial marketing,
however subject to forfeiture

The 180-day clock is triggered if the first applicant
markets the product subject to the certification or
the listed drug-authorized generic
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180-Day Exclusivity Forfeiture

Forfeited if fails to market the later of

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The earlier of 75 days of effective approval of first applicant or 30
months after submission of application entitling 180 days, or
75 days after any applicant (first to file or other) has obtained Tentative
Approval and with respect to each patent subject to first applicants IV
certification and at least one of the following has occurred:
 Infringement action brought against or a declaratory judgment
brought by which results in a court from which no appeal can be
taken (Court of Appeals) finding that patent invalid, not infringed or
not enforceable
 A court signs a Settlement or Consent Decree and enters a final
judgment finding invalid or not infringed*
 The patent information is withdrawn by the holder of the 505(b)
application
* Teva Pharmaceuticals v. FDA (October 2005)
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180-Day Exclusivity Forfeiture



The first applicant withdraws its application or
FDA considers application to have been
withdrawn
The first applicant amends or withdraws IV
Certification for all patents qualifying for 180day exclusivity
Failure of the first applicant to obtain
Tentative Approval within 30 months after the
date filed unless failure due to change in
review requirements
26
180-Day Exclusivity Forfeiture
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
Agreement with another applicant re
marketing for which FTC or Attorney General
files a complaint and there is a final judgment
from which no appeal can be taken that the
agreement violates anti-trust laws
All patents as to which applicant submitted a
certification for qualifying for 180-day
exclusivity have expired
27
Declaratory Judgment Action
re Patents
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Conditions as necessary to pursue:
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After Paragraph IV notification 45 days have
expired with no suit
If based upon non-infringement made an offer as
part of notice of confidential access to ANDA for
determining whether action should be brought
within 45 days
No damages allowed
MMA doesn’t change standard – still must show
reasonable apprehension of suit
28
Counterclaims
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In an infringement action may seek counterclaim to
correct or delete listing because patent
inappropriately listed
No damage
No independent cause of action
29
Non-Patent Exclusivity

5-Years New Chemical Entity


New Chemical entity – no active moiety (molecule
(excluding salts or esters) responsible for
physiological or pharmacological action) has been
approved by FDA in any 505(b) application
May not submit an ANDA or 505(b)(2) until
exclusivity has expired, except

May submit in 4 years if contains a Paragraph IV
Certification
30
Non-Patent Exclusivity
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3-Year Exclusivity
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Applies to (b)(1) & (2) and Original and Supplements
Application may be filed but effective approval cannot
issue until exclusivity expires
Scope (dosage form, dosage regimens)
31
Non-Patent Exclusivity

3-Year Exclusivity

Conditions:

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New clinical investigations (human studies (other than
bio) which have not been relied upon by FDA to
demonstrate substantial evidence of effectiveness or
safety in a new population)
Essential to approval (not duplicate or otherwise not
essential)
Conducted or sponsored by the applicant (filed 1571,
provided substantial support (50% or more of funding)
or predecessor in interest)
32
Authorized Generic

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The NDA holder authorizes a generic to
market product under its NDA
Court have upheld validity*
Can dilute the effectiveness of 180-day
exclusivity
FTC and Congress reviewing
* Teva Pharmaceutical v. Crawford (6/3/05, Ct of Appeals)
* Mylan Pharmaceuticals v. FDA (9/29/05)
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Conclusion
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