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ï Prior to 1962, approval by USFDA was on the basis of safety profile alone.

ï In 1962, Kefauver-Harris Amendments made to the Federal Food, Drug, and Cosmetics

Act added a new and compulsory requirement of ´proof-of-efficacyµ.

ï DESI program.

ï To get the USFDA approval, new drugs manufacturers were required to conduct

clinical trials on a limited number of human individuals so as to determine the

efficacy and safety of the new drugs and submit the results of the same to the USFDA

along with their New Drug Application (NDA).

 "-" ,-

ï Innovator company secure patent rights over their drug molecules in the early development

stage.

ï The discovery and development of new drug incurs a lot of monetary expense, efforts and time.

ï The effective patent term for which the manufacturer can recoup the investment and reaps

benefits gets reduced because of:

1] Developing the drug into a dosage form

2] Time taken to generate safety and efficacy data.

3] USFDA approval to market requires another couple of years.

 "-" )-

ï reneric companies were also required to carry out their own safety and efficacy
studies i.e. clinical trials.
ï Due to the high costs involved in conducting clinical trials, only a few generic
companies showed interest.
ï A generic drugs company was not allowed to begin the required USFDA approval
process for a generic drug until the patents on the corresponding innovator drug had
expired.
ï Consequently, patent protection for the innovator drugs used to unduly get extended
by two to three years.
ï This discouraged the entry of generic drugs in the market.
&'./+"

ï Drug Price Competition and Patent Term Restoration Act was passed by the
Congress in 1984 to overcome the above mentioned problems as well as to
address the inadequacies in the pharmaceutical regulatory system.

"0,&'./

ï Reducing the cost associated with the approval of a generic drug.

ï Allowing Early-Experimental-Use of the patented drug.

ï Compensating the branded drugs manufacturers for the time lost from the
patent term because of the regulatory approval formality
ï Motivating the generic drug manufacturers

ï To strike a balance between the interests of branded drug manufacturers,

generic drug manufacturers and the consumers.
 )+,&'./
ï Although the HWA provides a safe harbor from patent infringement, it requires generic drugs
manufacturers to engage in a specialized certification procedure.
ï Under the provisions of the HWA a generic drugs firm must certify its intentions with respect
to each patent associated with the generic drug it seeks to market.
For a generic drug manufacturer to submit ANDA, four possibilities exist under HWA:

‡ That patent information on the drug has not been filed i.e. no patent
Para I information appears in the orange book.

‡ That the patent has already expired.

Para II

‡ The date on which the patent will expire.

Para III

‡ That the patent is invalid or will not be infringed by the manufacture, use
Para IV or sale of the drug for which the ANDA is submitted.
 ,$-++
ï An ANDA certified under paragraphs I or II is approved immediately after meeting all
applicable regulatory and scientific (efficacy, safety and bioequivalence)
requirements.
ï A Para III filing is made when the ANDA applicant does not have any plans to sell the
generic drug until the original drug is off patent. ANDA approval under para III
certification is made effective from the date of patent expiration.
ï An ANDA applicant filing a paragraph IV certification must notify the proprietor of the
patent. The patent holder may bring a patent infringement suit within 45 days of
receiving such notification. If the patent owner timely brings a patent infringement
charge against the ANDA applicant, then the USFDA suspends the approval of the ANDA
until:
1] the date of the court·s decision that the listed drug patent is either invalid or not
infringed;
2] the date on which the listed drug patent expires, if the court finds the listed drug·s
patent is infringed; or
3] the date that is 30 months from the date the owner of the listed drug·s patent
received notice of the filing of a Paragraph IV certification. (Subject to modification by
the court).
 -,

ï The first generic applicant to file a paragraph IV certification is awarded a

180-day market exclusivity period by the USFDA. The 180-day market
exclusivity period ordinarily begins on the earlier of two dates:
1] The day the approved generic drug is first commercially marketed; or
2] The day a court decision holds that the patent which is the subject of the
certification is invalid or not infringed.
ï A successful defense of a patent infringement suit is not necessary to obtain
this exclusivity period.
ï Paragraph IV litigations: The issues that arise in ANDA patent infringement
litigation are generally the same as those which arise in other patent
litigations. One exception is that a patent holder usually cannot recover
monetary damages in an ANDA case because the infringement is prospective
in nature.
 123
 /'m"+

ï Warner²Lambert was founded as a drug store in 1856 in Philadelphia by

William R. Warner.
ï Pfizer took over Warner²Lambert in 2000.

2-/ +. +

ï +. is a Canadian pharmaceutical corporation. Founded in 1974, the
company is the largest producer of generic drugs in Canada, with sales
exceeding one billion dollars (CAD) a year. The company produces more than
300 generic pharmaceuticals in approximately 4000 dosages, exporting to
over 115 countries around the globe
2+$444

K

 

§

Novel Methods for Treating
Neurodegenerative
Diseases

m

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 $-" m"
1

  +  

4024175 Cyclic Amino Acids claimed the compounds Expired

(product patent) (including rabapentin)
(used in neurodegenerative
[ ¶175 patent ] method patent ¶479.)

4087544 Treatment of disclosed and Expired in

(epilepsy method Cranial claimed a method of treating may 1995
patent) Dysfunctions using certain forms of epilepsy
Novel Cyclic Amino using the compounds
[ ¶544 patent ] Acids claimed in the ¶175 patent
(and used in the ¶479
patent,) again including
rabapentin.
4894476 rabapentin a specific crystalline form of Expired in
(monohydrate Monohydrate and rabapentin monohydrate may 2008
patent) a Process for
Producing the
[ ¶476 patent ] Same

5084479 Novel Methods for use of certain cyclic amino acid Expires on
(neurodegenerativ Treating compounds,one of them being 23 nov 2010
e method patent ) Neurodegenerativ rabapentin, for the treatment of
e Diseases neurodegenerative diseases
[ ¶479 patent ] such as stroke, Alzheimer's
disease, Huntington's disease,
Amyotrophic Lateral Sclerosis
(ALS), and Parkinson's disease.
m"()"+
ï Lambert sold rabapentin under the trade name Neurontin.
ï In 1993, Lambert obtained approval for NDA from USFDA for
marketing rabapentin adjunctive therapy in the treatment of partial
seizures with and without secondary generalization in adults with
epilepsy, one of the several indications claimed in the expired
epilepsy method patent ¶544.
ï Significantly, the FDA did not approve rabapentin for any additional
uses, let alone for the uses claimed in the ¶479 neurodegenerative
method patent.
 +./),)"+

ï Apotex filed an ANDA under the HWA at the USFDA on April 17, 1998,
seeking approval to market a generic formulation of rabapentin for
the same indication for which Lambert's Neurontin was approved,
i.e., for "adjunctive therapy in the treatment of partial seizures with
and without secondary generalization in adults with epilepsy.
â"  +

ï Along with the bioavailability/bioequivalence test data required to be included

in its ANDA, Apotex filed a paragraph IV certification, declaring that its
proposed manufacture, use, and sale of rabapentin would not infringe either
the monohydrate patent ¶476 or the neurodegenerative method patent ¶479.
ï According to Apotex, its formulation would be anhydrous (i.e., would not
contain water), and would accordingly be outside the scope of the
monohydrate patent ¶476.
ï Moreover, Apotex declared that its pharmaceutical product's labeling does not
include any indication for use in the treatment of either neurodegenerative or
neurogenerative diseases.
ï Because all of the claims of the neurodegenerative method patent ¶479 were
directed to a use of rabapentin in the treatment of neurodegenerative
diseases, Apotex argued that the manufacture, use, or sale of its rabapentin
products would not infringe the neurodegenerative method patent ¶479.
 +5 m"

ï As required by the HWA, Apotex notified Lambert that it had filed the ANDA and
paragraph IV certification.
ï Also, Apotex provided in its notice letter a detailed statement of the factual and
legal basis for its opinion of non-infringement of the neurodegenerative
method patent ¶479.
ï It explained that its indicated use for its pharmaceutical product is partial
seizure and that the ¶479 patent does not claim a method of using gabapentin
and its derivatives for partial seizure.
 m"-5 +. +

Apotex moves for summary judgement

m"/

ï USFDA does not regulate the uses for which doctors prescribe drugs once
they are approved;
ï More than three-quarters of the prescriptions written by doctors for
Lambert's Neurontin are for indications other than epilepsy, including the
treatment of neurodegenerative diseases, and
ï Doctors, health care organizations, and other institutions commonly and
routinely substitute generic drugs for all indications for which the branded
drug is used.
ï Apotex knows and expects that its generic rabapentin will be prescribed by
doctors for all the same reasons they prescribe Neurontin including the
treatment of neurodegenerative diseases.
The District Court denied Apotex·s
motion.

Apotex again moved for summary

judgment, and the district court
granted that second motion.

Matter moved to federal court and

was resolved.
/

when the matter moved to the Federal Circuit, it was

concluded that it is not an act of infringement to submit an
ANDA for approval to market a drug for a use when
´ neither the drug nor that use is covered by an existing
patent,
´ and the patent at issue is for a use not approved under
the NDA.
ïù

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