ANDA

PARA IV & 505(b)2

 Hatch-Waxman Act

• Drug Price Competition and Patent Term

Restoration Act

• Approval of generic drugs

• Associated conditions
• Market exclusivity
• Rights of exclusivity
• Patent term extension
• Orange Book Listing  
 Para IV
The patent has not expired but the
applicant certifies that the patent is invalid
or is not infringed by its product.

Time limit for informing patent owner:
The company filing ANDA under para IV
must submit full and complete
information over and above what is
necessary under current law and must
notify the patent owner within 20 days.
If patent holder doesn’t sue within 45 days
then FDA may approve ANDA & the
applicant is entitled to 180 days of
exclusivity period

If patent holder sues within 45 days, this Non-extension of the 30-month

action automatically triggers a 30 month period
stay in FDA action

YES FDA may approve ANDA; first generic

30 month applicant is entitled to 180- day
stay expires exclusivity

NO
 505(B)(2) :APPLICATIONS

Differentiate From INNOVATOR

• Dosage form
• Strength
• Route of administration
• Substitution of an active ingredient in
a combination product
• Formulation
• regimen
 505(B)(2) :APPLICATIONS

• Dosing
• Active ingredient
• Combination product
• Indication
• Rx/OTC switch
• Naturally derived or recombinant
active ingredient
• Bioinequivalence
 Patent Term Extension

 Patent owner is entitled to the full

scope of a patent

 Allows PTEs based on the amount

of time a drug spends in the FDA
review process

 PTE cannot exceed five years

Amlodipine : Case Study

v/s
 Amlodipine : Case Study

• 1986 : Pfizer was granted a

patent

• The patent covered the molecule

amlodipine, including its salts
– amlodipine besylate
– amlodipine maleate.
 Amlodipine : Case Study

• 1987 : Pfizer filed another application

for amlodipine besylate salt
specifically

• Superior in treating hypertension

• Marketed it as Norvasc
 Amlodipine : Case Study

• Patent's expiry date approached

(Feb, 2006),

• Pfizer went ahead and filed PTE

 DRL FILED 505(b) 2

• DRL filed an new drug application

(NDA) for same under USFDAs
505(b) 2.

• Seeking marketing approval after it

was found the PTE by Pfizer was
only for amlodipine besylate.
 PFIZER SUES DRL

• October, 2002 USFDA granted approval

to DRL to go ahead

• Pfizer sued DRL for patent infringement

• Insisting that PTE covered the entire

scope of amlodipine.
 CASE VERDICT

• Pfizer lost the case in a New Jersey

district court in Dec.2002

• Won the same in a higher court in

Feb.2004  
 DR. REDDY'S ARGUMENT

• Dr. Reddy's argues that Pfizer's

term extension is limited to
amlodipine as the besylate salt, and
that amlodipine maleate is a
different "active ingredient."
 Dr. REDDY'S ARGUMENT

• Dr. Reddy's concedes that both products

have the identical "active moiety," as it
must in order to use Pfizer's approved
registration.

• Dr. Reddy's argues that only the specific

salt for which Pfizer obtained approval is
protected by the extended term of the
patent.
 PFIZER'S ARGUMENTS

• DRL application relied on the safety

and efficacy data submitted to the
FDA by Pfizer, which had included
testing of amlodipine as both the
maleate and besylate salts.
 PFIZER'S ARGUMENTS

• PTE contemplated that a therapeutic

product could be administered as a
"salt or ester of the active
ingredient,"
• The extension is not defeated by
simply changing the salt or ester.
• Pfizer stresses that the FDA's
approval describes the approved
product as "amlodipine."
 PFIZER'S ARGUMENTS
• Pfizer points out that a changed salt
does not affect the therapeutically
active agent, which is the same
amlodipine, whatever the salt.
 FINAL VERDICT

• Thus it was concluded that the

active ingredient is amlodipine, and
that it is the same whether
administered as the besylate salt or
the maleate salt.
 IPR issues

1. Extension of IPP

 Even after expiry of patents, IP

protection can be extended to
compensate for the loss to the
innovator during the approval process.

 Presently, this extension period is

restricted to five years.
 IPR issues

2. Broad nature of IP coverage

 DRL was not granted permission to

manufacture amlodipine besylate (AmVaz)
even though the Drug had not been covered
under the PTE.

 DRL followed necessary legal procedures

and even won in a lower court, but
ultimately did not get permission.  
 IPR issues

3. IPR issues extend to generics also

 DRL simply wanted to make a drug

whose patent term had expired and
which the original patent company had
not marketed at all.

 Still it was unable to get permission.

 GLAXO Vs CIPLA

Patent granted to GSK’s biggest selling asthma

drug Seretide also called Advair having global
sales of US $2.2 billion was challenged by the
generic drug makers on grounds of obviousness

12/08/21
 GLAXO Vs CIPLA

The main grounds on which the patent rested

was whether an inventive step was involved in
combining two older drugs, Flovent and
Serevant to make Advair

12/08/21
 GLAXO Vs CIPLA

The combination was entirely obvious and

cancelled the patent. The victory for generic
drug makers meant that they could launch
cheaper versions of the inhaled asthma
treatment as early as October, 2005 .

12/08/21