FDA - Patent Term Extension & Hatch-Waxman Act

FDA- Patent Term Extension - Legal
avenues for Generic Player
HATCH-WAXMAN ACT
SWAPNA SUNDAR
CEO, IP DOME – IP STRATEGY ADVISORS
(c) swapna sundar, IP Dome, 2012
DRUG PRICE COMPETITION

AND PATENT TERM
RESTORATION ACT OF 1984
Pub. L. No. 98-417
Codified at 15 U.S.C. §§ 68b-68c, 70b (1994); 21
U.S.C. §§ 301 note, 355, 360cc (1994); 28 U.S.C. §
2201
IMPORTANT CONCEPTS
Definitions and understanding
Pioneer/innovator drugs vs. Generic drugs

• Brand name/ pioneer/ • copies of brand-name drugs that have
innovator drugs are exactly the same dosage, intended use,
drugs which are patent effects, side effects, route of
protected. administration, risks, safety, and strength
• Brand names are as the original drug. In other words, their
usually capitalised such pharmacological effects are exactly the
as Lopressor same as those of their brand-name
counterparts.
• Names are not capitalised such as
metoprolol
• Should not look identical to brand name
drugs
• Can have different colours, flavours, or
combinations of inactive ingredients, but
active ingredients must be the same as
brand name drug.
Drug pricing is controlled by Federal Trade Commission

Some important terms

• Formulation is the process in which different chemical
substances, including the active drug, are combined to produce
a final medicinal product.
• Dosage forms are a mixture of active drug components and
nondrug components and include pill, tablet, or capsule, drink
or syrup.
• An active ingredient (AI/API) An active ingredient is any
component that provides pharmacological activity or other
direct effect in the diagnosis, cure, mitigation, treatment, or
prevention of disease, or to affect the structure or any function
of the body of man or animals.
• Drug Product is the finished dosage form that contains a drug
substance, generally, but not necessarily in association with
other active or inactive ingredients.
Contd.
• A Reference Listed Drug (RLD) is an approved drug
product to which new generic versions are compared to
show that they are bioequivalent.
• A New Molecular/chemical Entity is an active ingredient
that has never before been approved for marketing in US
by FDA.
• The strength of a drug product tells how much of the
active ingredient is present in each dosage.
• Drug products classified as therapeutically equivalent can
be substituted with the full expectation that the substituted
product will produce the same clinical effect and safety
profile as the prescribed product.
(c) Swapna Sundar, IP Dome
Product
- The active ingredient of a new human/animal drug,
antibiotic drug, or human/vet. biological product
- Any medical device, food additive or color additive
subject to regulation under the Federal Food, Drug and
Cosmetic Act
A patent is considered to claim the product if it

a. claims the active ingredient per se, or
b. claims a composition or formulation which contains the
active ingredient(s) and claims the composition or
formulation approved for commercial marketing or use
if any one active ingredient has not been previously
approved, it can form the basis of an extension of patent term
provided the patent claims that ingredient
DRUG APPROVAL Vs. DRUG PATENTING
FDA Center for Drug Evaluation and Research (CDER)

ensures that drugs marketed in US are safe and effective.
CDER does not test drugs. Innovator Co. is responsible for

testing and submitting evidence of safety and efficacy.
Office of Testing and Research conducts limited research in

the areas of drug quality, safety, and effectiveness.
A team of CDER physicians, statisticians, chemists,

pharmacologists, and other scientists reviews the sponsor's
NDA containing the data and proposed labelling.
Types of FDA applications

FDA: US Food and Drug Administration
• IND: Investigational New Drug Application
• NDA: New Drug Application
• ANDA: Abbreviated New Drug Application
• 505(b)(2) application
Balancing Innovation with Affordability
“ . . . the American
people will save money,
and yet receive the best
medicine that
pharmaceutical science
can provide.”
We have now just enshrined, as
soon as I sign this bill, the core - President Reagan, Sept.
principle that everybody should 24, 1984
have some basic security when
it comes to their healthcare.
- Barack Obama
Market share of generics

Generic Markets outlook 2015

Key findings and highlights
• The generics industry represents an integral element of the

broader prescription pharmaceutical market. This role as the
‘commoditizer’; however, the level of sales growth achieved
will not be sustainable.
• Sales growth will slow due to a fundamental change in the

growth strategies implemented by branded players - Big
Pharma in particular – which have become characterized by
a smaller number of blockbuster launches and increased
investment in biologics and vaccines.
HATCH-WAXMAN ACT
Basics
provisions
• Patent challenges and generic exclusivity
• Patent term extension
• Exemption to infringement: safe harbour
Key Features of the Hatch-Waxman Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy regulatory

approval process
• Non-patent exclusivity for innovators and generics
• Framework for patent notification and litigation

Why Hatch-Waxman Act?
• Efficacy: 1962 amendments to FDCA in

Response to the THALIDOMIDE issue,
first introduced proof of Safety and
efficacy requirements.
• Counter the lengthy approval period for innovators

Which resulted in de facto shortening of the patent term
• Counter the onerous approval requirements for generics

which resulted in “off-patent” drugs with no generic
competition
FDA approval
• Regulatory approval-time and cost

• Focus of FDA approval process-safety and efficacy
• Difference between the conditions for patentability and
approval
• Only one out of every 2,500 patents make it to the market
What products are included?

• human drug products: active ingredient of a
new drug or human biologic product
• medical devices
• food additives, or colour additives
• and animal drug products (Generic Animal Drug

and Patent Term Restoration Act (Public Law
100-670) 1988)
PATENT TERM
ADJUSTMENT
Patent Term Guarantee Act of 1999, a part of the
American Inventors Protection Act.
3 bases for adjustment:

1994 amendment 35 U.S.C. § 154: extended patent
term to 20 years
USPTO failure to take certain actions within

specified time frames (35 U.S.C. § 154(b)(1)(A))
USPTO failure to issue a patent within three years of

the actual filing date (35 U.S.C. § 154(b)(1)(B))
Delays due to interference, secrecy order, or

successful appellate review (35 U.S.C. §
154(b)(1)(C))
Provides day-for-day adjustment for each failure or
delay resulting in adjustment
Failure to act within specified time frames (14-4-4-4):
 on the application within fourteen (14) months of

filing/national stage entry
 on a reply or appeal within four (4) months of filing
 on an application within four (4) months after appeal if

allowable claims remain in the application
• In some instances, a remand shall be considered a decision
reversing an adverse patentability determination
 Failure to issue the patent within four (4) months of the

date the issue fee was paid and all outstanding
requirements were satisfied
Contd.
USPTO failure to issue a patent within three years of the
actual filing date:
 In an international (PCT) application, “actual filing date”

in 35 U.S.C. § 154(b)(1)(B) means the date national
stage processing commences
 The three-year period does not include time consumed

by any of Continued examination, Secrecy order,
interference, or any appellate review, or
– Applicant-requested delays
applicability
The PTA rules only apply to original applications filed on or after May
29, 2000.
PCT applications are not eligible but US national stage applications

are.
Reissue patents are not eligible for PTA because their term is fixed by
the term of the original patent.
PTA cannot extend the term of a patent beyond the date established
by a terminal disclaimer filed in that patent.
Limitations on adjustment
16 38
0 14 36
 No adjustment beyond any date
specified in a terminal disclaimer
 No double counting of overlapping
delays. Days to be calculated as
calendar days.
Applicant Adjustment Reductions
Reductions can occur when the applicant “failed to

engage in reasonable efforts to conclude processing or
examination of an application for the cumulative total of
any periods of time in excess of 3 months that are take
not respond to a notice from the Office beyond three
months making any rejection, objection, argument or
other request.” (35 U.S.C. § 154(b)(2)(C)).
Regulations define failure to engage in reasonable

efforts to conclude processing or examination of an
application. 37 C.F.R. 1.311 Notice of Allowance for fee
due within 3 months.
27
Impact
37 C.F.R. § 1.704(c)(1)-(11) provides for a reduction in the

PTA accumulated because of Office delays, e.g.,
suspension of action or deferral of issuance of a patent an
applicant’s request;
(2) abandonment of an application or delay in filing a

petition to withdraw abandonment holding;
(3) converting a provisional to a non-provisional and
(4) submission of papers after notice of allowance.

When is PTA determined

The USPTO sends a PTA calculation to the applicant twice
during prosecution of an application. The first time is with
the notice of allowance and issue fee due. The PTA
calculation is performed shortly before the notice is
mailed. The calculation includes an assumption that the
patent will issue within four months of issue fee payment.
The USPTO performs a second PTA calculation when the

patent is about to issue for inclusion on the face of the
patent. The second calculation includes consideration of
the time period from payment of the issue fee to issuance
of the patent.
Judicial review of USPTO determination
 Applicant (patentee) has 180 days from

patent grant to seek review of the
USPTO’s adjustment determination by
civil action at the US Distt. Court for DC
 No third party challenge to USPTO

determination prior to patent grant
PATENT TERM
RESTORATION
Formula
Computation
31
Patent Term Restoration

• Who: submitted by patent owner or his agent (35
U.S.C. § 156(d)(1)).
• When: filed with the relevant FDA Director within

the sixty-day period beginning on the date the
product received permission for commercial
marketing or use (35 U.S.C. § 156(d)(1)).
• What: contents of the application contain

information as per 35 U.S.C. § 156(d)(1)(A)-(E).
The New Drug Development Process:
Steps from Test Tube to New Drug Application
Review
Formula Under 35 USC §156
 50% of the time spent in initial clinical trials

(IND);
PLUS
 100% of the time spent in new drug application
(NDA) approval process
 Not the same as Patent Term Adjustment which

is a USPTO process for adding day-for-day
credits to patent term based on prosecution
delay. This is offset by applicant delay. Extn can
be in addition to adjustment
Patent Term Restoration under 35 USC §156
Maximum extn: No more than 5 years, or
amounting to a total of 14 years from date of
FDA approval (14 Y marketing time). If the
product has 14 years to go from marketing, no
extn. Can be granted.
Other requirements: Patent should not have

expired
 No previous extension under this provision
 First permitted commercial marketing or use
35
Statutory Requirements for Patent Extension

The patent claims the product, or a method of using the
product or a method of manufacturing the product (35 U.S.C.
§ 156(a)).
The term of the patent has not expired before the application
for PTE has been submitted (35 U.S.C. § 156(a)(1)).
The term has never been extended under 156 before (35
U.S.C. § 156(a)(2)).
The product has been subject to a regulatory review period

before its commercial marketing or use (35 U.S.C. §
156(a)(4)).
Patent and Exclusivity Search Results from query on Appl No 021366
Product 002 in the OB_Rx list.
Patent Data
Drug Drug Patent

Prod Patent Delist
Appl No Patent No Substance Product Use
No Expiration Requested
Claim Claim Code
021366 002 6316460 Aug 4, 2020 Y
021366 002 6858618 Dec 17, 2021 U-618
021366 002 RE37314 Jan 8, 2016 Y
Exclusivity Data
Appl No Prod No Exclusivity Code Exclusivity Expiration
021366 002 NCE Aug 12, 2008
021366 002 I-573 Nov 6, 2011
021366 002 I-547 Nov 8, 2010

Example timeline: rosuvastatin
06/12/92 440 patent filing date
11/9/93 440 patent issues
8/9/98 IND becomes effective

8/27/98 reissue application
6/26/01 NDA filed

8/7/01 Re 314 patent issues
8/12/03 NDA approved - product marketing

begins
generic applicant first-to file date

8/12/07
12/9/07 infringement suits filed
8/12/08 NCE marketing exclusivity expires
2/10/10 trial scheduled

2/12/11 30 month automatic stay expires
6/12/12 Original patent expiration date
patent expiration date following

1/8/16 extension
CASE LAW
Restoration and adjustment
Case
• A patent that claimed a metabolite of an approved drug
was held not to claim the approved drug, even though the
court recognized that use or sale of the metabolite would
have infringed the patent claiming the approved drug
product- Hoechst-Roussel Pharmaceuticals Inc. v.
Lehman, 109 F.3d 756, 759 (Fed. Cir. 1997)
Other conditions
• A patent is only eligible for one term extension, so term
extension is effectively available for only one product per
patent
• The product must have been subject to regulatory review
before its commercial marketing or use, and the resulting
permission for commercial marketing or use must be the
first granted
Summary
• A patent can be extended only once
• Patent must claim the active ingredient of the approved
product
• One extension per regulatory review period
• Extension only applicable to the approved product, not all
the claims of the patent
42
Cases deciding issues in Patent Term Extn

Limitations on amount of term extension:
-Includes only time after patent issue date (35 U.S.C. § 156(c)).
-Time where applicant failed to exercise due diligence is
subtracted (35 U.S.C. § 156(c)(1)).
-Only one-half of the testing phase is counted (35 U.S.C. §
156(c)(2)).
-The total market exclusivity time of a drug cannot exceed 14
years, regardless of how much time was lost to clinical testing
and regulatory review. (35 U.S.C. § 156(c)(3)).
-The total time of extension is limited to no more than 5 years
(35 U.S.C. § 156(g)(6)).
43
Case 01: Ortho-McNeil v. Lupin (603 F.3d 1377 (Fed. Cir. 2010))
Is a patent claiming a specific enantiomer eligible for patent

term extension when a racemate of the enantiomer was
previously approved?
Yes, a patent claiming the specific enantiomer may be

extended under 35 U.S.C. § 156 even though the racemate
of the enantiomer was previously approved and a patent
claiming the racemate received extension.
44
Case 02: Photocure v. Kappos (603 F.3d 1372 (Fed. Cir. 2010))
Is a patent claiming an ester of a previously approved

active ingredient eligible for patent term extension?
Yes, the statutory language recites, “active ingredient

including any salt or ester of the active ingredient,” not
active moiety.
Glaxo II (894 F.2d 392 (Fed. Cir. 1990) is controlling in that

the term “product” in 156(a)(5)(A) means “active
ingredient,” that is, the substance physically present in the
final dosage form.
45
Case 03: The Medicines Company v. Kappos (E.D. Va. 1:10CV286)
Patent Term Extension

- Does the term “date” as used in section 156(d)(1)
(“beginning on the date. . . .”) refer to a business day or
calendar day?
Medicines Company argues business day. Government

argues calendar date. Case is pending.
46
Case 04: Wyeth v. Sebelius (603 F.3d 1291 (Fed. Cir. 2010))
When does the approval phase begin for a new animal

drug application when the parts of the application are
submitted on a rolling basis?
• The approval phase begins when the

Administrative New Animal Drug Application is submitted
to FDA referencing all the previously submitted and
approved application components.
Wyeth V. Kappos
• Where periods of delay overlap, the net adjustment is
limited to ‘the actual number of days the issuance of the
patent was delayed,’ to prevent double counting.
• Thus according to PTO, a patentee was due only the

greater of one delay not both.
• Federal Circuit held that though double counting should

be avoided, the language of the statute was unambiguous
that both delays must be counted unless they fall on the
same calendar day.
NEW DRUG PRODUCT

EXCLUSIVITY
1. Patented drugs
2. Generics
New Drug Product Exclusivity
Exclusivity Regardless of Existence of Patent
 NCE (New Chemical Entity): 5 years

 New active ingredient, new molecules, new salts
 FDA cannot accept a generic application for 5 years (4
years if a Para IV challenge)
 Effectively 7 ½ years if there is a Para IV challenge after
4 years
 New product/new use /supplemental exclusivity: 3 years

 (new clinical studies to support a new indication,
formulation, salt, dosage regimen, etc.; enantiomers)
New chemical entities (NCE)
505(b)(1) or New Drug Applications

• Contains full reports of investigations
of safety and effectiveness
• Five year exclusivity
505(b)(2) Application
• At least some of the information required for
approval comes from studies not conducted by or
for the applicant
Continued
 Orphan Drug: 7 years
 If FDA approval is for disease affecting less than

200,000 U.S. citizens & tropical diseases eg.
Myeloma/glioma in adults & muscular dystrophy in kids
 Pediatric use: 6 months in addition to existing exclusivity

or patent term:
 Must have written request from FDA
 Must report studies to FDA
 Must fulfill request conditions
Esomeprezole
Montelukast
Pancrelipase
505 (b)(2) Drug

♦ Not a generic and not totally new
♦ Similar, but with limited differences, to previously approved
drug
♦ Variation of previously approved drug(s) containing the same
active Moiety
Changes such as Dosage form, Strength, Delivery mechanism,

Different formulation (e.g., different salt, complex, enantiomer,
new combination of previously approved drugs)
Hatch-Waxman:
♦ 505(b)(2) - Streamlined approval process for new products
with same active moiety as previously approved drug
– Reference listed drug (RLD) Must provide safety and
effectiveness studies but can rely on published scientific data
Examples 1
New Delivery Mechanism
– Canasa® (mesalamine) suppositories – Axcan
– ClobexTM (clobetasol proprionate) lotion – Galderma
– LuxiqTM (betamethasone valerate) foam - Connetics
– TestimTM (testosterone) gel – Auxilium
♦ New Dosage Form

– AltoprevTM (lovastatin) extended release tablets - Andrx
– DepoDurTM (morphine Sulfate) liposomal injection – Skye
Pharma
– Doxil® (doxorubacin HCl) liposomal injection
Examples 2
♦ New Formulation
– PexevaTM (paroxetine mesylate) tablets – Synthon
– Stalevo® (carbidopa/levodopa/entacapone) tablets – Orion
– Xopenex® (levabuterol HCl) inhalation – Sepracor
♦ New Indication
– Avodart® (dutasteride) capsules – GlaxoSmithKline:
urinary condition –benign prostatic hyperplasia /male pattern
baldness
– Thalomid® (thalidomide) capsules – Celgene: for cancer
GENERIC CHALLENGES TO
PATENT VALIDITY
Orange Book
Requirements for generic approval
NDA ANDA
1. Chemistry 1. Chemistry
2. Manufacturing
2. Manufacturing
3. Controls
3. Controls
4. Labeling
4. Labeling
5. Testing
6. Animal Studies 5. Testing
7. Clinical Studies 6. Bioequivalence
8. Bioavailability
Patent linkage
• Generic Marketing Approval is “Linked” to
the Expiration of the Pioneer Drug Patent
• If a patent exists, marketing approval will
not be granted to a generic until the patent
has expired or is found to be invalid.
• Orange Book patent listings: New Drug
Application (NDA) must include patent
information and the FDA considers the
existence of patents as part of the approval
process for certain drug applications
What is Experimental use?

In Roche Prods., Inc. v. Bolar Pharm.
Co.(1984) held that scientific inquiry that has
"definite, cognizable, and not insubstantial
commercial purposes" did not qualify as
experimental use. Bolar used ‘valium’ to test
bioequivalence of its generic version.
In Embrex, Inc. v. Service Engineering Corp.

(2002)that the experimental use defense applied
only to actions performed "for amusement, to
satisfy idle curiosity, or strictly for philosophical
inquiry."
The experimental use defense
• It could never have been the intention of the legislature
to punish a man who constructed such a machine merely
for philosophical experiments
• Thus where it is made or used as an experiment, whether
for the gratification of scientific tastes, or for curiosity, or
for amusement it is not infringement
Bolar exception
• Roche Products V. Bolar Pharmaceutical Co. (Fed. Cir.
1984). Roche was the assignee of the rights, expiring in 1984
in prescription sleeping pill "Dalmane” –
• U.S. Patent No. 3,299,053 (the '053 patent), which expired on

January 17, 1984 - Novel 1 and/or 4-substituted alkyl 5-
aromatic-3H-1,4-benzodiazepines and benzodiazepine-2-
ones
• In early 1983, Bolar decided to market a generic drug

equivalent to Dalmane after patent expiry. Bolar immediately
began its effort to obtain federal approval and to prove bio-
availability. Took steps to acquire flurezepam HCl for studies
on stability etc. required for ANDA filing.
• Because a generic drug's commercial success is
related to how quickly it is brought on the market
after a patent expires, and because approval for
an equivalent of an established drug can take
more than 2 years, Bolar, not waiting for the '053
patent to expire, immediately began its effort to
obtain federal approval to market its generic
version of Dalmane
• In mid-1983, Bolar obtained from a foreign manufacturer 5
kilograms of flurazepam hcl to form into "dosage form
capsules, to obtain stability data, dissolution rates,
bioequivalency studies, and blood serum studies"
necessary for a New Drug Application to the FDA
Infringement (the Bolar exception)
• Roche complained before Distt. Ct. that testing 6
m before expiry constituted infringement. Does
the limited use of a patented drug for testing and
investigation strictly related to FDA drug approval
requirements during the last 6 months of the term
of the patent constitute infringement?
• Held: Tests, demonstrations, and experiments

which are in keeping with the legitimate business
of the alleged infringer are infringements for
which experimental use is not a defense
Infringement:
• 271(a) : Whoever without authority makes, uses or sells
any patented invention, within the United States during
the term of the patent therefore, infringes the patent
• The patentee does not need to have any evidence of
damage or lost sales to bring an infringement action
The Court held that..
• Tests, demonstrations, and experiments which
are in keeping with the legitimate business of the
alleged infringer are infringements for which
experimental use is not a defense
• Bolar's intended "experimental" use is solely for
business reasons and not for amusement, to
satisfy idle curiosity, or for strictly philosophical
inquiry
“Safe Harbor” for pre-approval activities
Before the Act, a generic manufacturer who used a

patented drug during the patent term for the purpose of
conducting tests to submit information to the FDA
committed patent infringement
Roche Products v. Bolar, 733 F.2d 858 (Fed. Cir. 1984)

Submitting an ANDA with a PIV certification is infringement
35 USC § 271 (e)(2): It shall be an act of infringement to
submit -
(A) an application under section 505(j) of the Federal Food,
Drug, and Cosmetic Act or described in section 505(b)(2)
of such Act for a drug claimed in a patent or the use of
which is claimed in a patent, or
(B) … if the purpose of such submission is to obtain approval
under such Act to engage in the commercial
manufacture, use, or sale of a drug or veterinary
biological product claimed in a patent or the use of which
is claimed in a patent before the expiration of such
patent.
“Safe Harbor” for pre-approval activities
 Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193
(2005)
 statutory text “provides a wide berth for the use of patented

drugs in activities related to the federal regulatory process”
 use of patented compounds in preclinical studies is protected .

. . as long as there is a reasonable basis for believing that the
experiments will produce “the types of information that are
relevant to an IND or NDA.”
Safe Harbour Provision
35 USC § 271:
(a) direct infringement
(b) induced infringement
(c) contributory infringement
(e)(1) It shall not be an act of infringement to make, use, offer

to sell, or sell within the United States or import into the United
States a patented invention solely for uses reasonably related
to the development and submission of information under a
Federal law which regulates the manufacture, use, or sale of
drugs or veterinary biological products.
Framework for patent notification and
litigation
 NDA holder must notify FDA of any patent that claims

a drug or method of using a drug and with respect to
which a claim of infringement can reasonably be
asserted
 FDA publishes
in “Orange Book”
Notice Letter
 Generic applicant who files a paragraph

IV certification must notify the patent and
NDA holder with a detailed statement
 Patent/NDA holder has 45 days to sue
 Generic applicant can file a declaratory

judgment action if not sued
Generic applicant patent certifications
ANDA Certification Patent status
Paragraph I: No Patent info in Orange

Book
Paragraph II: Patent expired
No product launch until

Paragraph III: patent expires
Patent is invalid,
unenforceable, or will not be
Paragraph IV: infringed by the
manufacture, use, or sale of
the drug product for which
the ANDA is submitted
Certifications
• Section 505(j)(2)(A)(vii)
• (1) That such patent information has not been
filed;
• (2) That such patent has expired;
• (3) That the proposed drug will not be marketed
until expiration of the patent.
• (4) That either the proposed generic drug does
not infringe the patent or the patent is invalid.
This is known as Paragraph IV certification.
Para I to IV
• If the applicant makes a certification under paragraphs
I or II, the statute provides that the FDA may approve
the ANDA effective immediately
• If the applicant makes a certification under paragraph

III, the FDA may approve the ANDA effective on the
date that the applicant certifies that the patent will
expire
• Paragraph I, II, III certifications relatively

straightforward
– Existence of ANDA normally a secret until
approval date
• Paragraph IV certification more

complicated to administer
– ANDA applicant must notify innovator
company of its filing; must describe
reasons patent will not be infringed, is
invalid, or unenforceable
• When an applicant makes a certification under
paragraph IV the statute begins by providing a
forty-five-day window during which the patent-
holder may bring suit against the applicant
• If the patent-holder brings suit during that forty-
five-day period, the statute says that the FDA's
approval of the ANDA must be delayed for thirty
months
• Paragraph IV Certification
– Innovator has 45-days after receipt of notice to

file an infringement suit; the submission to FDA
of paragraph IV certification in an ANDA
creates infringement for purposes of federal
court jurisdiction
– If lawsuit filed FDA approval is stayed for 30-

months; at end of period FDA issues tentative
approval
• Provision that is intended to allow the patent-holder time
to vindicate its patent in court
• If the court finds that the patent is invalid or is not
infringed, the FDA's approval becomes effective as of the
date of that ruling
Automatic Stay of FDA Approval
“somewhat artificial” act of infringement that vests
district courts with jurisdiction - Eli Lilly & Co. v. Medtronic,
Inc., 496 U.S. 661 (1990)
Initiation of Lawsuit means FDA cannot approve an ANDA

until:
 Final court ruling;
 Patent expires; or
 30 months from notification

Remedies for infringement
§ 271(e) (4) For an act of infringement described in paragraph (2)
(A) the court shall order the effective date of any approval of the
drug involved in the infringement to be a date which is not earlier
than the date of the expiration of the patent which has been
infringed,
(B) injunctive relief may be granted against an infringer to prevent

the commercial manufacture, use, offer to sell, or sale within the
United States or importation into the United States of an
approved drug or veterinary biological product, and
grant injunctive relief;
(C) no damages unless there has been commercial manufacture,

use, or sale .
…except that a court may award attorney fees under section 285.
Most ANDA applicants await resolution of the

litigation before going to market to avoid
liability for damages
• Provision that is intended to allow the patent-holder

time to vindicate its patent in court
• If the court finds that the patent is invalid or is not

infringed, the FDA's approval becomes effective as of
the date of that ruling
Basis for invalidity
• Anticipation
• Obviousness
• Prior art date to be kept in mind
• Combining two references-motivation to combine
• When a reference cannot be used as prior art
against the challenged patent
• Species and genus situations
• Obviousness type double patenting
Bases for Non-infringement
• All Elements Rule
• Pennwalts case
• – Estoppel
• Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki
Co., Ltd., 234 F.3d 558, 56 U.S.P.Q.2d 1865 (Fed. Cir.
2000)
• Designing around a valid US patent -
Professor Keyton’s approach.
Para IV Certification & Patent Litigation
(summary)
• Notice to the patent holder
• Legal and factual basis
• Non-infringement or invalidity
• 45 day period to bring suit
• Stay of approval
• 30 month period
• Judgment of the court
180 days Market Exclusivity
• Section 505(j)(5)(B)(IV)
• First to file
• When does it start
• Judgment trigger
• Commercial marketing trigger
Mova v Shalala & the successful defense
requirement
• FDA approved an application by a drug manufacturer,

Mylan Pharmaceuticals, Inc. to market a generic version
of micronized glyburide, a drug used to treat diabetes
• Mova Pharmaceutical Corp. had filed an earlier

application to market a generic version of the same drug
Second filer’s application approved
• Mova's application had not yet been approved, because

of a patent infringement suit brought by Pharmacia &
Upjohn Company
• Upjohn claimed that Mova's product infringed a patent

belonging to Upjohn
180-day exclusivity
• When Mova learned that the FDA had approved Mylan's

application, it brought suit relying on 21 U.S.C.
355(j)(5)(B)(iv) (1994), to compel the FDA to delay the
effective date of this approval until 180 days after the
earlier of the dates that Mova won its suit or began to
market its product
Successful defense
• Mova argued that it was entitled to 180-day market

exclusivity period running from the date Mova won its suit
or began marketing its product, and the FDA was barred
from approving Mylan's similar application until after the
end of that 180-day period
• In response, the FDA cited a regulation- The successful

defense requirement
Implication
• 355(j)(5)(B)(iv) seems to grant exclusivity to the
first to file irrespective of whether he has been
successful in the infringement suit or not
• FDA argues that a literal reading would produce
absurd consequences
• FDA’s interpretation was that the first Paragraph

IV applicant was required to have “successfully
defended against a suit for patent infringement”
before the applicant is eligible for the 180-day
marketing exclusivity period
Where the applicant is never sued
• (1) cases in which the first applicant is never
sued, and (2) cases in which the first applicant
loses its suit
• If the first applicant is never sued, the FDA
claims, then the court-decision trigger will never
be satisfied
• Later ANDA applicants will be unable to market
their products until the first applicant decides to
put its product on the market
Collusion with innovator
• The first applicant could in theory wait indefinitely
to begin selling its product, and thereby block all
sales by later applicants
• If the first applicant colludes with the pioneer drug

company to eliminate generic competition, or if
the first applicant is simply unable to obtain FDA
approval of its production facilities and so cannot
put its product on the market
First applicant loses its suit
• If the first applicant loses its infringement suit, the first
applicant would then be able to satisfy neither the court-
decision trigger nor the commercial-marketing trigger
• Thus, the FDA claims, no generic drugs could enter the
market until after the pioneer company's patent expired
First applicants who lose their suit
• FDA's current regulations suggests a possible

way of addressing this problem
• That regulation provides that, if an ANDA

applicant who makes a certification under
paragraph IV later loses its patent-infringement
suit, it must amend its ANDA to make a new
certification under paragraph III
Arguments against the requirement
• The Practical effect of the FDA’s regulation is to write the

commercial-marketing trigger out of the statute
• It serves the public interest to permit a prudent ANDA

holder in that situation to stay off the market until the
litigation is resolved, thereby minimizing potential
damages
Successful defense impact
• The successful-defense requirement, according to the

FDA, is calculated to eliminate both occurrences. An
applicant that is never sued or that loses its suit will
not have "successfully defended” against a suit for
patent infringement
Intention of the law
• Congress may have intended to reward the first
ANDA applicant for his enterprise whether or not
he is later sued
• The statutory scheme only runs into problems if
the first applicant never starts selling his product.
An alternative might be to prescribe a period
within which a first applicant who has not been
sued must bring his product to market in order to
benefit from the exclusivity period
PATENT LINKAGE AND ABUSE OF

PROCESS
What is linkage?
How does it operate?
Patent challenges and generic exclusivity
Overview of the legal process- ANDA Requirements:
• Information to show that that the listed drug is

approved;
• That the listed drug has the same active ingredient as
the new drug;
• That the route of administration, the dosage forms,
the strength of new drug etc are the same as the
listed drug;
• That the new drug is bio-equivalent to the listed drug.
Eight major parts to the FDA's review of generic drug:

There should be RLD listed brand-name drug.
Generic must have the same active ingredient and the same labeled strength.
It must have the same dosage form-tablets, patches and liquids are examples of
dosage forms.
It must be administered the same way, for example, swallowed as a pill or given as
an injection.
The manufacturer must show the generic drug is "bioequivalent" to RLD drug
The generic drug's labeling must be essentially the same RLD drug.
Fully documented chemistry, manufacturing steps, and quality control measures.
Each step of the process must be detailed for FDA review.

The raw materials and the finished product meet US

Pharmacopoeia standards for drug purity in US.
Generic drug maintains stability as labelled and must

continue to monitor the drug's stability. The firm must show
that the container and its closure system won't interact with
the drug.
Full description of the facilities to manufacture, process, test,

package, label and control the drug. It must certify that it
complies with FDA regulations and undergo inspection of the
manufacturing facility to assure compliance.
Before FDA approves a generic drug, it usually conducts an

inspection to ensure the firm can manufacture the product
consistently.
Orange book
1) Lists:
1) Approved Drugs,
2) Discontinued Drugs
3) Provides Patent and Exclusivity Information
2) Published annually with monthly cumulative
supplements
• Electronic Orange Book also available.
• When generic drug companies inform FDA that it does not
believe a particular listed patent does covers the FDA-
approved drug product - FDA requests evaluation of
complaint by innovator company
• Innovator company can request de-listing or respond with
good-faith belief that listing is proper
Listing example
Active Ingredient Search Results from "OB_Rx" table for query on

"rosuvastatin."
RL Dosage Form; Proprietary

TE Code Active Ingredient Strength Applicant
Appl No D Route Name
021366 No ROSUVASTATIN 10MG CRESTOR IPR
TABLET; ORAL
CALCIUM
TABLET; ORAL
CALCIUM
021366 Yes ROSUVASTATIN 40MG CRESTOR IPR
TABLET; ORAL
CALCIUM
TABLET; ORAL
CALCIUM
Listing example 2
Lists Product Name
Patent Number Patent Expiration Date Exclusivity
Information
Listing procedure
• Under 505 (b) and (c) of the FDAC Act, patent
information covering the drug must be
submitted within 30 days of approval of NDA /
supplement or within 30 days of grant of patent
– US FDA Requires Applicant to list patents that
cover the drug as part of NDA filing
– Applicant Must submit signed declaration
– FDA relies on innovator drug company’s assertion
– Patent information published in Orange Book
Abuse of listing provision
• Listing irrelevant patents

• The '84 Act does not prevent an NDA
holder from listing a newly acquired
patent
• This further delays generic competition
• Only one thirty month stay proposed
• Shared Exclusivity
BIO-EQUIVALENCE
generic applicants must scientifically demonstrate that their

product is bioequivalent (i.e., performs in the same manner)
to the pioneer drug.
measure therate and extent of absorption-or bioavailability-

of the generic drug: time it takes the generic drug to reach
the bloodstream and its concentration in the bloodstream in
24 to 36 healthy, normal volunteers.
Brand-name drugs are subject to the same bioequivalency

tests as generics when their manufacturers reformulate
them.
Section 505(j)(2)(A)(vii)
• Generic Drug Company must certify when filing
Abbreviated New Drug Application (ANDA)
1) That the drug has not been patented;

2) That the patent has already expired;
3) The date on which the patent will expire, and the
generic drug will not go on the market until that date
passes; or
4) That the patent is not infringed or is invalid
Referred to as paragraphs I, II, III and IV

Certifications as in slide 62 above
First applicants who enter into an
agreement with the NDA holder
• First ANDA applicant to file a patent challenge
may never trigger the start of the 180-day period,
thereby blocking the FDA from granting approval
to any generic product.
• First generic challenger will enter into a lucrative
cash settlement with the patent owner that results
in a judgment in favor of the patent
• Ex: Hoechst-Roussel v Andrx
• Literal reading of the section sought to be avoided by the
FDA
• But that would prevent a person who has done a good job
in designing around and thus avoided suit from entering
the market- Purepac v. Friedman
Improper listing of patents
• The orange book
• Holders of NDAs to identify all patents claiming
an approved drug product or a method of using
such a product
• As to which a claim of patent infringement might
reasonably be asserted
• Must update list within 30 days of receiving
relevant patent.
• Provided no guidance whatsoever as to what patents
should or should not be listed and no mechanism for
determining if a patent was properly or improperly listed
• Court has held that FDA performs purely ministerial
function in listing patents
• There is no cause of action to de-list a patent alleged to
be improperly listed
• Abuse of listing provision
• Listing irrelevant patents
• The '84 Act does not prevent an NDA holder from listing a
newly acquired patent
• This further delays generic competition
• Only one thirty month stay proposed
• Shared Exclusivity
180 days Market Exclusivity
• Section 505(j)(5)(B)(IV)
• First to file
• When does it start
• Judgment trigger
• Commercial marketing trigger
• FDA’s interpretation was that the first Paragraph IV applicant

was required to have “successfully defended against a suit for
patent infringement” before the applicant is eligible for the 180-
day marketing exclusivity period. Court refused to accept FDA
reading.
If the first applicant is never sued, the FDA claims, then the
court-decision trigger will never be satisfied. Later ANDA
applicants will be unable to market their products until the first
applicant decides to put its product on the market.
• Court’s “wait and see” approach: grants exclusivity to the
generic that is first in-time to file an ANDA, and then requires
• the FDA to stay any subsequent ANDA until the first-filer
resolves its suit
Court decision trigger satisfied by a
subsequent applicant
• The 180-day exclusivity period never starts. No
subsequently filed ANDA can be approved unless a final
judgment adverse to the patent is obtained by one of the
subsequent applicants.
• Even if the patent is subsequently challenged and
declared invalid, the benefit will go to the first to file
180-Day Exclusivity Forfeiture
Generic exclusivity is forfeited 75 days after any of the

for failure to market upon the following with respect to
any applicant with tentative
later of:
approval:
– Court decision that the
patent is
The earlier of: invalid or not infringed (no
– 75 days after approval of the further
first appeal)
applicant’s ANDA – Settlement order or consent
– 30 months after the date of decree with judgment of
ANDA invalidity
submission or noninfringement
– Patent listing is withdrawn
Decision of a court
• Interpretation of "court decision"
• FDA’s interpretation: “Court Decision” is the final decision
of a court
• The Tor Pharm and Mylan case: decision of any court
finding in favour of ANDA filer satisfies the trigger
First applicant loses its suit

• If the first applicant loses its infringement suit, the first
applicant would then be able to satisfy neither the court-
decision trigger nor the commercial-marketing trigger
• Thus, the FDA claims, no generic drugs could enter the

market until after the pioneer company's patent expired
First applicants who enter into an

agreement with the NDA holder
• First ANDA applicant to file a patent challenge
may never trigger the start of the 180-day period,
thereby blocking the FDA from granting approval
to any generic product.
• First generic challenger will enter into a lucrative

cash settlement with the patent owner that results
in a judgment in favor of the patent
Hoechst-Roussel v Andrx : H-R, the patentee reached a

settled with Andrx in respect of once-daily diltiazem product
developed by Andrx allegedly infringing upon a formulation
patent for Hoechst Marion Roussel's Cardizem CD a once-
daily medication for the treatment of hypertension and
angina. Andrx developed a second formulation that did not
infringe on the Hoechst Marion Roussel patent. Andrx has
agreed to market this second formulation and to not market
the first. Andrx delayed marketing the formulation until the
suit was settled. Hoechst Marion Roussel agreed to
compensate Andrx for that delay and will make a final lost-
profit payment of approximately $50 million to Andrx. (June
1999)
TOTAL No. OF LAW SUITS AGAINST INNOVATORS: 749

INVOLVING :243 brand-name drugs.
72% of Para IV challenges result in litigation
Generic challenger wins: 42%
Average loss for innovator companies: 12%
Average life of patents shortened by: 4 years
Between 2008-2009, after 58 ANDA filings, Indian generic maker

Orchid Chemicals & Pharmaceuticals Ltd has received approvals from
the US Food and Drug Administration (US FDA) for its antibiotic
combination piperacillin and tazobactam for injection, with 180-day
exclusivity to market the products in US.
Dr. Reddy’s marketed generic versions of Omeprazole, and Prozac with

180 day exclusivity.
With 27 pending ANDAs, Ranbaxy won this month to sell generic

Lipitor, and will share the exclusivity with Israeli generic Teva.
2000 -June 2008: 200 Originator – generic settlement

agreements to resolve patent disputes or opposition
procedures covering 49 medicines, of which 63% were best-
selling medicines that lost
exclusivity between 2000 and 2007.
In 48% of cases, the generic company's ability to market its

medicine was restricted.
In addition to the restriction in many cases - a value transfer
from the originator to the generic company in the form of a
direct payment, a license, a distribution agreement or a "side-
deal".
Direct payments to generic companies in more than 20

settlement agreements for a total amount exceeding € 200
million
http://ec.europa.eu/competition/sectors/pharmaceuticals/inquiry/2_Originator_Generic_competitio
n.pdf
Para IV strategies
• In the last 10 years, generic companies have made the
Para IV certification a routine part of doing business.
• Generic players usually targets blockbuster drugs which
has a large market potential and a patent position that
could be challenged.
• The strategy of filing P-IV seems to be to file P-IV’s as
soon as four years after a product launches (NCE-1).
Possible Generic Paragraph IV Strategies
Targets • Market Position

• Everything • • First filer
• Blockbusters • • Subsequent filer
• Niche Products • – Limited competition
– Formulation • – Highly competitive
– Therapeutic Class market
– Limited API
– Limited Sales
• Line Extension
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
Most generics interact closely with (c) Swapna Sundar, IP Dome
originator drug manufacturers –

sometimes with respect to specific 1. Teva
drugs, and at others on more general 2. Mylan
drug development
3. Sandoz
4. Watson
5. Greenstone
6. Pan Pharma
7. Hospira
8. Apotex
9. Mallincrodt
(covidien)
10. Dr. Reddy’s
ANDAs are filed by generics that have an agreement with originator
 not to be sued, but to be supplied with generic copy of drug
Both generic and originator benefit without competition or fear of litigation
 a long term relationship develops between originator and generic
Pfizer licensed the product to its own Greenstone subsidiary for generic
Gabapentin (Neurontin).
Examples of this relationship include:
Paxil (Paroxetine) - licensed by GSK to Par

Prozac (Fluoxetine) - licensed by Lilly to Barr
Augmentin (Co-Amoxiclav) licensed by GSK to IVAX
In February this year Dr. Reddy's announced a similar deal with Merck & Co.
for two products Proscar (Finasteride) and Zocor (Simvastatin).
Apotex Inc. v. Daiichi Sankyo, Inc., Nos. 2014-1282,

2014-1291 (Fed. Cir. Mar. 31, 2015)
• Daiichi listed two patents covering Benicar® No. 5,616,599,
covers the active ingredient of the drug, and expires on April
25, 2016 with pediatric exclusivity and No. 6,878,703, covers
methods of treatment, and expires on November 19, 2021.
• In April 2006, Mylan filed an ANDA with a paragraph IV
certification that both the ’599 and ’703 patents were invalid or
not infringed by Mylan’s proposed generic drug. In July 2006,
for reasons that remain unexplained, Daiichi disclaimed all
claims of the ’703 patent, as permitted under 35 U.S.C. § 253.
Daiichi then sued Mylan for infringing the ’599 patent.
• Apotex, Inc. sued Daiichi for a declaratory judgment of non-
infringement of a Daiichi-owned, but Daiichi-disclaimed, patent.
Purdue Pharm. Products v. TWI Pharms.,

No. 12-5311 (D.N.J.)
• Purdue holds the NDA for Intermezzo®, a drug used to
treat middle-of-the-night insomnia. Four patents are listed
in the Orange Book in connection with the NDA. By the
time TWi filed its ANDA, four other ANDAs had already
been filed and presumably at least one of those is entitled
to 180-day exclusivity. Purdue sued TWi on only two of
the patents, and granted TWi a covenant not to sue on the
other two. TWi filed a DJ counterclaim for
noninfringement of all four Orange Book-listed patents.
• TWi's DJ counterclaim is important because it "could
potentially trigger the first ANDA filer's 180-day exclusivity
period. This would have the effect of expediting TWi's
ability to market its generic version of Intermezzo®."
COUNTER GENERIC STRATEGY

AstraZeneca received FDA approval to market Omeprazole
(exp. In 2001) in US in 1989, as Prilosec®. By 1999,
AstraZeneca’s product became one of the most widely
prescribed drugs of any kind in the world, with sales of some
$6.1 billion annually. In 1999 AstraZeneca commenced suit
against four generic pharmaceutical manufacturers after
ANDA filing and in 2000 against 4 more.
In 1995, the company decided to create a strategy to

overcome losses due to patent expiry.
What would the outcome be?

How can this strategy work?
US Patent 4255431 WO patent 94/27988

on omeprazole - on esomeprazole – s-
racemic mixture
Evergreening
enantiomer
Purple as
symbolics of
dependable
magic
Distress
resolution,
fear
reduction
“the purple pill”

the most popular strategy used to defend brands against generic competition(c) swapna
is the launchsundar, IP Dome,
of new product 2012
formulations
Counter generic strategies

• the most popular strategy is the launch of new product
formulations (82%)
• defensive pricing (70%) lowering prices or renegotiating
purchasing contracts to fight generics
• dependence on overall franchise strength and increased
marketing and promotion
• ATORVASTATIN: Ranbaxy has 180 days of exclusivity on

the market due to a settlement with Pfizer - launched
generic atorvastatin; competition Lipitor, and an offering
from Watson Pharmaceuticals, which is selling an
authorized generic version on behalf of Pfizer.
Pfizer strategy
• special contracts and increased product promotion, to
ensure consumers will find it easy and affordable to
remain with Lipitor for six months.
• deals to ensure benefits for links in the pharmaceutical
value chain. Pharmacy benefit managers have received
discounts on Lipitor
• customers co-pays have dropped to $4 through a Pfizer
program that provides a discount card.
• Pfizer has assured Congress that insurance companies
are also seeing these discounts though no numbers have
been given
Abbot strategy: Fenofibrate (TRICOR)

• Abbott dominates in the US despite the existence of generic
fenofibrate & questions regarding the drug’s efficacy in reducing
cardiovascular risk. Abbott's successful market dominance can be
attributed to 2 factors:
• The sequential launch of branded reformulations that used only
bioequivalence data in NDA. These reformulated products showed no
improvement in patient outcomes but made substitution with older generic
formulations impossible.
• Taking advantage of FDA 30-month stay, Abbott used this time to produce
and market their next-generation product before the generic version of the
previous-generation drug could be approved. Lacking the extensive sales
force of major pharmaceutical companies, generic drug makers could not
compete.
• Abbott has been the target of anti-trust lawsuits, including a class
action suit in 2005 by the Louisiana Wholesale Drug Company, and
various patients and states. All of these lawsuits were ultimately
settled out of court and cost Abbott $300 million, a figure that
amounts to less than 4% of total sales to date of their fibrate
franchise.
Thank you for your attention
Swapna Sundar
swapna@ipdome.in
Phone: 044-42116559
Hariprasad K.S.
hariprasad@ipdome.in
Phone: +91-
9841730474

FDA - Patent Term Extension & Hatch-Waxman Act

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FDA- Patent Term Extension - Legal

avenues for Generic Player

DRUG PRICE COMPETITION

Pioneer/innovator drugs vs. Generic drugs

Drug pricing is controlled by Federal Trade Commission

Some important terms

A patent is considered to claim the product if it

DRUG APPROVAL Vs. DRUG PATENTING

FDA Center for Drug Evaluation and Research (CDER)

CDER does not test drugs. Innovator Co. is responsible for

Office of Testing and Research conducts limited research in

A team of CDER physicians, statisticians, chemists,

Types of FDA applications

Market share of generics

Generic Markets outlook 2015

• The generics industry represents an integral element of the

• Sales growth will slow due to a fundamental change in the

• “Safe Harbor” for pre-approval activities

• Patent term restoration to offset lengthy regulatory

• Non-patent exclusivity for innovators and generics

• Framework for patent notification and litigation

• Efficacy: 1962 amendments to FDCA in

• Counter the lengthy approval period for innovators

• Counter the onerous approval requirements for generics

• Regulatory approval-time and cost

What products are included?

• food additives, or colour additives

• and animal drug products (Generic Animal Drug

3 bases for adjustment:

USPTO failure to take certain actions within

USPTO failure to issue a patent within three years of

Delays due to interference, secrecy order, or

Failure to act within specified time frames (14-4-4-4):

 on the application within fourteen (14) months of

 on a reply or appeal within four (4) months of filing

 on an application within four (4) months after appeal if

 Failure to issue the patent within four (4) months of the

 In an international (PCT) application, “actual filing date”

 The three-year period does not include time consumed

PCT applications are not eligible but US national stage applications

Applicant Adjustment Reductions

Reductions can occur when the applicant “failed to

Regulations define failure to engage in reasonable

37 C.F.R. § 1.704(c)(1)-(11) provides for a reduction in the

(2) abandonment of an application or delay in filing a

(3) converting a provisional to a non-provisional and

(4) submission of papers after notice of allowance.

When is PTA determined

The USPTO performs a second PTA calculation when the

Judicial review of USPTO determination

 Applicant (patentee) has 180 days from

 No third party challenge to USPTO

Patent Term Restoration

• When: filed with the relevant FDA Director within

• What: contents of the application contain

 50% of the time spent in initial clinical trials

 Not the same as Patent Term Adjustment which

Other requirements: Patent should not have

Statutory Requirements for Patent Extension

The product has been subject to a regulatory review period

Drug Drug Patent

021366 002 6316460 Aug 4, 2020 Y

021366 002 6858618 Dec 17, 2021 U-618