PATENTLY ABSURD:

Evergreening of pharmaceutical patent protection under the Patented Medicines

(Notice of Compliance) Regulationsof Canada’s Patent Act

ByEdward Hore,

Hazzard & Hore

PATENTLY ABSURD:

Evergreening of pharmaceutical patent protection under the Patented Medicines

(Notice of Compliance) Regulationsof Canada’s Patent Act

ByEdward Hore,

Hazzard & Hore

EDWARD HORE IS A COMMERCIAL LITIGATION LAWYER who practices almost exclusively in thearea of intellectual property with the firm Hazzard & Hore in Toronto. He was called to

the Bar in 1986. He frequently represents the Canadian Generic PharmaceuticalAssociation (CGPA) and generic drug manufacturers both in the courts and as a lobbyist,and has appeared before all levels of courts as well and before several parliamentary andsenate committees concerning the Patented Medicines (Notice of Compliance) Regulations. Heserved as counsel to CGPA in its consultations with the federal government on Bill C-9, theJean Chrétien Pledge to Africa. He writes widely on intellectual property law, and is a some-time columnist on intellectual property law for Lawyers Weekly and for many years wroteannual reviews of patent, trademark and copyright law for Canadian Lawyer magazine. Thisarticle has been reproduced and distributed by CGPA with the permission of the author.

Table of Contents

Executive Summary . . . . . . . . . . . . . 3

Highlights . . . . . . . . . . . . . . . . . . . . 5

Part I . . . . . . . . . . . . . . . . . . . . . . . . 6

Part II . . . . . . . . . . . . . . . . . . . . . . 20

Conclusion . . . . . . . . . . . . . . . . . . . 28

Footnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Appendix A . . . . . . . . . . . . . . . . . . . . . . . . . 32Appendix B. . . . . . . . . . . . . . . . . . . . . . . . . . 33Appendix C . . . . . . . . . . . . . . . . . . . . . . . . . 34Appendix D . . . . . . . . . . . . . . . . . . . . . . . . . 34Appendix E. . . . . . . . . . . . . . . . . . . . . . . . . . 35Appendix F . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Copyright © 2004 by Edward Hore

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2

Executive Summary

THE PATENTED MEDICINES (NOTICE OF COMPLIANCE) REGULATIONS

are regulations under Canada’s Patent Act that apply only topharmaceutical products. They give pharmaceutical patentees,

i.e. brand-name drug companies, extra remedies in a patent dispute,far beyond the normal remedies available to patentees in otherindustries. The Regulations have been described as “a draconianregime” by the Supreme Court of Canada in their effect on genericmanufacturers

The Regulations allow brand-name drug companies to keep ageneric competitor out of the market automatically for 24 months,without a court hearing, merely by starting a court case assertingthat a patent, or several patents, would be infringed by the genericproduct.

The Regulations have enabled many abusive strategies, which allowpatentees to prolong their market monopolies at the expense of allpurchasers of prescription medicines in Canada, including provincialgovernments, employers that sponsor drug plans and the public.Unfortunately, brand-name companies now find it more lucrative tolitigate than to innovate. Examples of these strategies are describedin detail in Part II.

The Regulations give patentees every incentive to litigate patents aslong as possible, keeping non-infringing, lower-cost generic pharma-ceutical products off the market. Generic drug companies win mostof the cases eventually, but only after years of delays.

The automatic stay under the Regulations is particularly problemat-ic because loopholes in the wording of the Regulations allow brand-name drug companies to obtain several automatic stays in a row, asnew patents are listed under the scheme, a practice known as “ever-greening.”

Health-care commissioner Roy Romanow called on the federalgovernment to review this practice in his November 2002 report. InFebruary 2004, the Competition Bureau made the same recommen-dation.

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In April 2001, the Senate Standing Committee on Banking, Tradeand Commerce noted that the Regulations may not be working asParliament originally anticipated and that the courts are fully capa-ble of determining appropriate procedures in patent disputes, whichshould not differ substantially from one industry to another.

In December 2003, the United States amended its drug patentscheme to limit brand-name drug companies’ ability to employ ever-greening strategies to keep generic competition off the market.

Repealing the Regulations would not violate Canada’s internationalobligations; patent disputes would simply be litigated via the normalcourt process used in patent disputes in all other industries.

In short, brand-name drug companies should not be granted auto-matic extensions of their market monopolies simply because theydecide to sue a generic pharmaceutical manufacturer.

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Highlights• Pharmaceutical products with annual sales totalling nearly $1-

billion in Canada have had their market monopolies extendedby evergreening strategies under the Patented Medicines(Notice of Compliance) Regulations.

• Brand-name drug companies have employed strategies underthe Regulations to extend their exclusive marketing rights onblockbuster drugs such as anti-depressant Paxil, heartburndrug Losec and Taxol, the leading treatment for breast, ovari-an and lung cancer.

• Since 1998, generic pharmaceutical manufacturers have wonat least 75% of the cases under the Regulations. However, evenwhen the generic firm wins the court cases, the brand-namedrug company has successfully extended its market monopoly,sometimes for years after the expiry of the basic patents.

• Multiple-patent strategies are increasingly used by brand-namecompanies to extend their market monopolies beyond theexpiry of the patent on the basic medicine. As evidence ofthis, Health Canada approved only 16 new active substancesin 2003, yet brand-name drug companies added 103 patents toHealth Canada’s Patent Register in that same year.

• Under the Regulations, brand-name drug companies areallowed to list patents for uses of a drug, even though the drugis not approved for that use by Health Canada. Patents can belisted to restart the automatic stay even years after the basicpatent on the drug has expired.

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THE PATENTED MEDICINES (NOTICE OF

COMPLIANCE) REGULATIONS givepharmaceutical patentees (brand-

name drug companies) powerful reme-dies in a patent dispute, in addition tothe normal remedies under the PatentAct available to patentees in other indus-tries.

The Regulations were enacted undersection 55.2 of the Patent Act in 1993.1

They were amended in 19982 and againin 1999.3

The procedureunder the Regulations,in short, allows apatentee to keep ageneric competi-tor out of the mar-ket automatically,merely by assert-ing that a patent,or several patents,would be infringed by the generic prod-uct.

The Regulations were originally enact-ed for the dual purpose of protectinglegitimate patent rights and acceleratingthe market entry of affordable genericdrugs. Rather than protecting legitimate

patent rights, however, the Regulationshave enabled a host of abusive strategiesthat allow patentees to prolong theirmarket monopolies at the expense of theCanadian public. Examples of such strate-gies are described in detail in Part II.

In practice, the Regulations do notfacilitate the market entry of affordablegeneric drugs, but rather tie up genericmanufacturers in years of wasteful andineffectual litigation over dubious

p a t e n t s .Throughout the liti-gation, the genericmanufacturer issubject to automat-ic injunctions pre-venting its lower-cost product fromentering the mar-ket, long past thetime when its drug

has been found safe and effective byHealth Canada.

The Regulations give patentees everyincentive to litigate meritless patentclaims as long as possible, keepingaffordable, generic products off the mar-ket. The public pays higher drug prices

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Absurd Practices:Constructing the thicket of patents

Part IThe Patented Medicines (Notice of Compliance) Regulations

”The anti-generic strategy bypharmaceutical companies hasprobably the highest rate ofreturn of any business activitythey do right now.”

Stock Analyst Hemant K. Shah, Wall Street Journal, July 12, 2001.

as a result.

The Regulations have been describedas “a draconian regime” by the SupremeCourt of Canada in their effect on gener-ic manufacturers.4

The Regulations could be eliminatedwithout violating any of Canada’s treatyobligations. If the Regulations were abol-ished, pharmaceutical patentees wouldstill have all the legal rights that otherpatentees do, but they would no longerhave an automatic right to keep com-petitors off the market.

Brand-name drug companies shouldnot be granted automatic extensions oftheir market monopolies simply becausethey decide to sue a generic firm.

The procedure under the Regulations

The procedure under the Regulations,in brief, is as follows:

The register: Patentees, referred to as“first persons,” may list patents on apatent register in connection with drugproducts for which they hold regulatoryapproval.5 The health and safety regula-tor at Health Canada, TherapeuticProducts Directorate (TPD), maintainsthe register.

Allegation: If a generic manufactur-er, referred to as a “second person,” filesa submission that makes a comparisonor reference to the first person’s drug, i.e.is an Abbreviated New Drug Submission(ANDS), the Minister of Health (in prac-tice, Therapeutic Products DirectorateTPD), the federal health and safety regu-lator, may not issue regulatory approvalunder the Food and Drug Regulations (a

notice of compliance or NOC) to thegeneric drug until the second person hasaddressed all listed patents. The secondperson must either accept that it will notget regulatory approval until expiry ofall listed patents,6 or serve an “allega-tion” on the first person that the listedpatent or patents are invalid or are notinfringed by its submission,7 togetherwith a detailed statement of the legaland factual basis of the allegation.8

Judicial review application: Thefirst person, or originator company, onbeing served with such an allegation,may within 45 days commence a judicialreview application for an order that theNOC not be issued to the generic drug.9

Automatic stay: If the application iscommenced, the NOC may not be issuedfor 24 months,10 or until the court hear-ing or patent expiry.11 As the FederalCourt of Appeal stated, “By merely com-mencing the proceeding, the applicantobtains what is tantamount to an inter-locutory injunction for up to 30 months[as the time frame then was] withouthaving satisfied any of the criteria acourt would require before enjoiningissuance of an NOC.”12

Prohibition order: At the hearing ofa judicial review application under theRegulations the court must determinewhether the generic manufacturer’s alle-gation is “justified.” If the court findsthe allegation is not justified, the courtmust issue an “order of prohibition,”preventing the Minister from issuing theNOC until patent expiry.13 If the courtfinds the allegation is justified, the appli-cation is dismissed, and health and safe-ty approval may be granted once the

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TPD’s regulatory review is complete(assuming no other prohibition applica-tions have been commenced in respectof the same generic drug submission,and no other patents are listed).

Litigation does not determinepatent issue: The litigation started bythe first person after receiving an allega-tion is not an action for patent infringe-ment, but a judicial review proceeding.14

Procedurally, the litigation consists of anexchange of affidavit evidence andcross-examination, followed usually by aone to three day hearing. Although suchjudicial review proceedings are theoreti-cally “summary” in nature, they maytake years to get to a hearing. The issueof patent infringement or validity can-not be determined in NOC proceedings;“their object is solely to prohibit theissuance of a notice of compliance underthe Food and Drug Regulations.”15

Therefore, the remedies under theRegulations are in addition to the reme-dies available under the Patent Act; eitherparty can also commence a patentaction on the same patent.16 As theFederal Court of Appeal observed,“patent invalidity, like patent infringe-ment, cannot be litigated in this type ofproceeding [i.e. an application under theRegulations]. I can only think that thedraftsperson had in mind the possibilityof there being parallel proceedings insti-tuted by the second person which mightgive rise to such a declaration [of inva-lidity or non-infringement] and be bind-ing on the parties.”17

The odd result is that a second per-son might lose the prohibition proceed-ings under the Regulations, i.e. be unable

to enter the market due to a prohibitionorder, yet later establish at a full trialunder the Patent Act that the patent isboth not infringed and invalid.18

Damages: If a generic product isdelayed by the Regulations, the genericmay be able to claim damages from thefirst person.19 However, there is no pro-vision in the Regulations for damages topayers such as provincial governments,private benefit plan operators or thepublic.

No damages have ever been awardedto any generic party under this section.There are now at least 12 section 8 casesbefore the courts, in which generics seekdamages resulting from delays to marketentry of generic drugs. It may take manyyears for these cases to be resolved.Many other generic drugs are nowdelayed by the Regulations, at great costto the public, but the delay is ongoing.Litigation for damages cannot be com-menced until an NOC is obtained,which may not occur for many years.

It is unlikely that the damages sec-tion will ever be a disincentive to theabusive use of the Regulations becausegeneric prices are much lower than thepatentee’s prices. Therefore any damagesor profits that generic parties are award-ed are likely to be far less than the wind-fall the patentee earned from using thestay to keep competition off the market.Furthermore, patentees argue in thesecases that section 8 is unconstitutional,and are seeking to have the courts strikeout the section so that they never haveto pay any damages.

As the Competition Bureau noted onFebruary 27, 2004: “Furthermore, I note

8

there is no ready mechanism for com-pensating consumers affected by thesedelays in the introduction of genericdrugs, thereby creating a possible incen-tive for brand-name pharmaceuticalcompanies to strategically use the NOCRegulations to improperly delay genericdrug entry."

Evergreening: Because the term“evergreening” implies perpetual renew-al, it is sometimes used to describe vari-ous strategies involving the use of theautomatic stay in the Patented Medicines(Notice of Compliance) Regulations (PM(NOC) Regulations) to prevent competi-tion after basic patent protection on adrug product has expired.

For the purposes of addressing ever-greening, the main points about theprocedure described above are:

• A 24-month stay on approval of ageneric drug occurs automatically if a

“first person,” a brand-name drugcompany, commences a prohibitionproceeding within 45 days of receiv-ing a notice of allegation (NOA) froma “second person,” usually, thoughnot always, a generic drug company.

• Even if a generic company is subjectto the 24-month stay as a result ofsuch a prohibition proceeding, itmust still address any other patentsthat the patentee may list on thepatent register.20

• If the second person addresses otherpatents by serving further NOAs, pro-hibition proceedings start the 24-month stay again.

This process can be repeated, allow-ing a patentee to use weak patents claim-ing coatings, crystalline forms, manufac-turing processes, new uses etc. to pre-vent competition.

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A Case Study

The Paroxetine Prognosis: Take nine patents and call me in 8 years

THE DELAY IN THE MARKET ENTRY OF A GENERIC DRUG can be considerable, as illus-trated by the following chronology in respect of paroxetine, an anti-depressant sold under the trade name Paxil.

• Generic pharmaceutical manufacturer Apotex filed an abbreviated submis-sion for Apo-paroxetine on August 29, 1997, and served Notices of Allegationto the four patents listed on the patent register at the time.

• SmithKline Beecham commenced two applications in response to the allega-tions (T-2660-96 and T-2230-97), triggering the stay.

• While those cases were before the court, SmithKline listed a further patent(the ‘637 patent), on February 17, 1998.

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• SmithKline’s two earlier applications were dismissed April 20, 1999,21 i.e. thecourt found Apotex’s allegations of invalidity and non-infringement werejustified, but Apotex was unable to obtain its NOC because the ‘637 patenthad meanwhile been listed.

• Apotex’s submission entered “patent hold” status on October 9, 1999, i.e.TPD’s health and safety approval process was complete.

• Apotex served an allegation that the ‘637 patent was invalid. SmithKlinecommenced a new application (T-677-99), re-triggering the stay. This appli-cation was dismissed on July 6, 2001;22 the Court found Apotex’s allegationof invalidity was justified.

• While the litigation on the ‘637 patent was pending, SmithKline added morepatents to the register.

• Apotex served an allegation to the ‘575 patent, resulting in a new prohibitionapplication (T-1059-01), triggering a further automatic stay. That case was dis-missed on May 30, 2003; the court found Apotex’s allegation of doublepatenting to be justified.23

• However, another prohibition proceeding had meanwhile been commencedagainst Apotex concerning three further patents on “Form A” (T-876-02).24

• Several generic companies finally received NOCs in October 2003, whenGenpharm, another generic company, also won prohibition proceedings onsome of the same patents already litigated by Apotex,25 and GlaxoSmithKlineseems to have decided that the risk of damages outweighed the benefit ofcontinuing to litigate.

A diagram of this chronology is set out in Appendix F.

Note that the delay in market entry of the Apotex product was about fouryears after the health and safety approval process was complete, yet the genericmanufacturers’ NOAs were found to be justified in every case that went to a hear-ing. In the third case mentioned above, T-1059-01, the court commented on thepatentee’s multiple-patent strategy as follows:

The effect of [the 24-month automatic stay] is to put in place a manda-tory injunction that remains in force until either the case is disposed ofor the 24-month stay expires. The addition of additional patents allowsthe patent-holder to bring additional applications, thereby obtainingmultiple injunctive periods. There is no need to look further than the caseat bar for an excellent example of this practice. Even though Apotex suc-cessfully invalidated the ‘637 patent in 2001, the filing of this applica-tion by GSK has prohibited Apotex from bringing its product to market

for the past two years.26

Similar evergreening strategies used for omeprazole capsules, citalopramtablets, diltiazem capsules and omeprazole tablets, are illustrated throughdiagrams provided in the appendices.

At least 75% of the prohibition applications decided by a court since1998 have been dismissed; that is to say, the generic won. But, as the aboveexamples show, even when a generic manufacturer “wins” several timeswith respect to a particular drug, further automatic stays may still keep itsproduct off the market.

The 75% figure is about the same as in the United States. The FederalTrade Commission studied equivalent litigation in the U.S. in 2002, andfound: “The data in the [FTC] study suggest that the generic applicantshave brought appropriate patent challenges: generic applicants prevailedin nearly 75% of the patent litigation ultimately resolved by a court decision.”27

As discussed below, the FTC study led to recent amendments to permitonly one stay in the U.S.

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Eligibility: What patents can be listed?

Given the extraordinary benefit tothe first person (brand-name drug com-pany) of listing as many patents as pos-sible over time, the rules governing theeligibility of patents for listing are ofcritical importance. A summary of therules as they stand follows.

Section 4 of the PM (NOC) Regulationsgoverns the filing of patent lists. Anexcerpt is set out below, with the moreimportant phrases highlighted.

Patent List

4. (1) A person who files or has fileda submission for or has been issued,a notice of compliance in respect ofa drug that contains a medicine maysubmit to the Minister a patent list

certified in accordance with subsec-tion (7) in respect of the drug.

(2) A patent list submitted in respectof a drug must…

(b)… set out any Canadianpatent that is owned by the per-son, that contains a claim forthe medicine itself or a claim forthe use of the medicine and thatthe person wishes to have includ-ed on the register;

(3) Subject to subsection (4), a per-son who submits a patent list mustdo so at the time the person files asubmission for a notice of compli-ance.

(4) A first person may, after the dateof filing a submission for a notice ofcompliance and within 30 days afterthe issuance of a patent that wasissued on the basis of an applicationthat has a filing date that precedes

the date of filing of the submission,submit a patent list, or an amend-ment to an existing patent list, thatincludes the information referred toin subsection (2).

(6) A person who submits a patentlist must keep the list up to date butmay not add a patent to an existingpatent list except in accordance withsubsection (4).

(7) A person who submits a patentlist or an amendment to an existingpatent list under subsection (1) or (4)must certify that

(a) the information submitted isaccurate; and

(b) the patents set out on thepatent list or in the amendmentare eligible for inclusion on theregister and are relevant to thedosage form, strength and routeof administration of the drug inrespect of which the submissionfor a notice of compliance hasbeen filed.

Broadly speaking, the restrictions onlisting patents in the case law, such asthey are, can be divided into two cate-gories which might be termed “subjectmatter” and “timing” restrictions. Bothcan be circumvented easily by the pat-entee.

Subject matter restrictions

Under section 4(2)(b), the patentmust contain a claim for the medicineitself or a claim for the use of the medi-cine.

”Pure” process claims are not claims

for the medicine itself (although prod-uct-by-process claims are), nor are claimsto intermediates i.e. substances used inthe manufacturing process,28 claims tometabolites,29 claims to medical devicessuch inhalers, patches or kits.30

Claims to compositions are claims tothe medicine itself.31 A compositionpatent, also known as a formulationpatent, is a patent claiming the activeingredient combined with one or moreinactive ingredients, for example a coat-ing. Such patents typically issue after theactive ingredient itself is old, and nolonger patentable. There can be manycomposition patents for a particulardrug product.

Starting about 1999, the Ministertook the position that patents claimingformulations that the brand is not itselfapproved to sell could not be listed.32

However, the Federal Court of Appeal, inEli Lilly, a 2 to 1 decision, held thatpatents on non-approved formulationscould be listed.33

The Eli Lilly case greatly increased theclass of patents that could be listedbecause the patentee can potentiallyobtain many patents for formulationscontaining the active ingredient; there isno end to the excipients, coatings, sol-vents and other variants that might beclaimed as novel.

The Courts have also said that apatent on a non-approved use is eligiblefor listing.34 In reaching that decision,Justice Blais commented that theRegulations are ambiguous with respectto patent eligibility, and that althoughhe was bound to apply the Eli Lillymajority decision, he found it “oppo-

12

site” to “logic”. He stated: “No doubtclearer language in the PM (NOC)Regulations would go a long way to dis-pel the fog we find ourselves in, and pre-vent the abundant litigation which issure to continue as long as the ambigui-ty remains."

The register includes patents on bothapproved and non-approved formula-tions and uses, products-by-process,variants such as allegedly new coatingsor dosage forms, manufacturing meth-ods using, for example, particular sol-vents or temperatures, dosing regimes,allegedly new crystalline forms, etc.There are as many as 11 patents on theregister for some products. A genericmanufacturer never knows when morepatents will be added to the register for agiven drug.

Timing restrictions

There are also timing rules on whennew patents can be listed, but again theyare so easily surmounted as to be effec-tively meaningless.

Under s. 4(4), a patent resulting froman application filed prior to the first per-son’s submission for a notice of compli-ance can be listed, if the first person sub-mits the patent within 30 days after thepatent issues. A “supplement to a newdrug submission” (SNDS)35 has been heldto be a “submission” for the purposes ofthis section.36

This broad reading of “submission”opens the door widely because a patent-ee can file an SNDS when it chooses; formost drugs new SNDSs will be submittedroutinely from time to time to update

the information filed with HealthCanada.

Section C.08.003(2) of the Food andDrug Regulations lists the circumstanceswhen an SNDS can be filed by a sponsor,and contains a long list of potentialchanges than can be effected by filing anSNDS, such as a change in the “descrip-tion of the drug,” the “brand name” ofthe drug, the “specifications of theingredients,” the “plant and equipmentused in manufacturing,” etc.

In Bristol-Myers Squibb, a case involv-ing an SNDS for a name change, theFederal Court of Appeal held that if theSNDS does not “change the drug,” thenthe SNDS cannot be used to list apatent.37 A subsequent trial level deci-sion refused to apply the Bristol-Myerscase,38 but was overturned on appeal.39 Amore recent case has held that an SNDSfor an additional manufacturing sitecannot support the listing of a patent.40

Because the wording of theRegulations is unclear, the courts havesaid in effect that a patent can be listedwith any SNDS not for a name change.The Federal Court of Appeal recentlyheld that even a seemingly minor prod-uct monograph revision (an addition ofa sentence indicating that the drug clar-ithromycin is also available packagedtogether with two other drugs) can beused to list an unrelated patent for amethod of crystallizing clarithromycinin a solvent.41 The patentee, AbbottLaboratories, has now listed eight morepatents for clarithromycin,42 and will nodoubt continue to list more. Severalautomatic stays have been commencedagainst various generic manufacturers.

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The Minister of Health has triedunsuccessfully to get the courts to pro-vide clarification as to the meaning ofthe wording in s. 4 of the Regulations. Inlate February 2002, the Minister com-menced a “Reference by FederalTribunal” under Rule 18.3(1), asking thecourts to rule to whether a patent mustbe “relevant” to the SNDS with which itis submitted. However, brand-name drugcompanies moved successfully to strikeout the Reference on the grounds thefacts put to the court by the Ministerwere in dispute.43

As noted above, the “filing date” ofthe patent must be prior to the “submis-sion.” Brand-name drug companiesargued that the words “filing date” insection 4(4) include a priority date,44 andinitially convinced TPD to adopt thatposition. But TPD then changed itsmind, and refused to list various patentswhere the priority date, not the filingdate, was prior to the submission,including a patent for azithromycin sub-mitted by Pfizer. Brand-name drug firmsthen commenced litigation against theMinister attacking this position, but thecourts held that “filing date” does notinclude a priority date.45 Pfizer’sazithromycin patent, the court said, wastherefore out of time to be listed.

However, Pfizer simply listed theazithromycin patent with a later SNDS,thus circumventing the time limit.

This example shows that if a patent-ee misses one time limit to list its patent,all it need do is file an SNDS, and its getsthe benefit of a later time limit. In short,nothing prevents brand-name drugcompanies from listing new patents for a

drug, and starting the automatic stayagain and again. All listed patents mustbe addressed by the generic company,regardless of what SNDS they were listedwith.46

Brand-name drug companies general-ly file many patent applications, so as tohave a steady supply of new patents tolist for any particular drug. Entering anyimportant drug as a search term in theCIPO patent database47 will typicallyturn up dozens of patents or open-to-the-public applications. For example, asearch of the term “omeprazole” onOctober 1, 2004 turned up 210 patentsor applications.

The number of patents listed onHealth Canada’s Patent Register underthe Regulations far exceeds the numberof new pharmaceutical productsapproved in any given period of time.For example, only 16 “new active sub-stances,” meaning new drugs, wereapproved by Health Canada in 200348

but 103 patents were added to the patentregister in the same year.49

The question arises: does this chaoticand unfair system serve the public inter-est in access to non-infringing, afford-able drugs?

Policymakers’ concerns

Various policymakers have expressedconcerns about the Regulations.

The Romanow Report of November28, 2002 referred to evergreening as aparticular concern affecting the cost ofdrugs:

Recommendation 41:

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The Federal government shouldimmediately review the pharma-ceutical industry practices relatedto patent protection, specifically,the practices of evergreening andthe notice of compliance regula-tions. The review should ensurethat there is an appropriate balancebetween the protection of intellec-tual property and the need to con-tain costs and provide Canadianwith improved access to non-patented prescription drugs.50

The reference to evergreening in therecommendation is explained as follows:

A particular concern with currentpharmaceutical industry practice isthe process of “evergreening,”whereby manufacturers of brandname drugs make variations toexisting drugs to extend theirpatent coverage. This delays theability of generic manufacturers todevelop cheaper products for themarketplace and is a questionableoutcome of Canada’s patent law.

The Report comments specifically onthe Regulations as follows:

Furthermore, regulations under thepatent law require generic drugmanufacturers to demonstrate thattheir product is not infringing on apatent held by another drug manu-facturer rather than putting theonus of the patent drug manufac-turer to show that their patent hasbeen infringed - what is referred toas the notice of compliance regula-tions. Suggestions have been madethat this leads to “pre-emptory”lawsuits from patented drug manu-facturers as a way of delaying theapproval of generic drugs. Clearly,if this is the case, the practice is not

in the public interest. The federalgovernment should review thisissue, determine what constitutes alegitimate extension of patent pro-tection, and also consider ways ofstreamlining approval of genericdrugs…51

At the resulting hearings before theHouse of Commons StandingCommittee on Industry, Science andTechnology in early June 2003, IndustryCanada (which drafted the Regulations)was, as usual, supportive of theRegulations in general, but also suggestedrecent court decisions dealing with thetiming of the listing of patents and therelevance of patents “require the balanceto be looked at carefully.”52

Throughout late 2003 and early2004, the government’s agenda on drugpatents became exclusively focused onBill C-9, The Jean Chrétien Pledge to Africa.The worthy objectives of that legislation,however, did nothing to resolve themounting problems with theRegulations.

More recently, the Commissioner ofCompetition commented that theGovernment may wish to review theRegulations:

… a number of court decisions overthe last several years regardingwhat constitutes a relevant patentand the time period during whichsuch a patent can be added havesomewhat altered the balance con-tained in the NOC Regulationsbetween the competing interests ofthe brand-name pharmaceuticalpatent holders and generic drugcompanies. Furthermore, I notethere is no ready mechanism in the

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NOC Regulations for compensatingconsumers affected by delays in theintroduction of generic drugs,thereby creating a possible incen-tive for brand name pharmaceuticalcompanies to strategically use theNOC Regulations to improperlydelay generic drug entry.

Therefore, from a competitionpolicy perspective in particular, theGovernment may wish to reviewthe current regulatory processestablished by the NOC Regulationsto ensure that an appropriate bal-ance be maintained between pro-tecting intellectual property rightsand encouraging a competitive sup-ply of pharmaceutical products forconsumers.53

The Senate has also expressed con-cern about the Regulations. On April 5,2001, the Senate Banking Committeecommented in its Observations on Bill S-17 that the Regulations “may not beworking in the manner that Parliamentoriginally anticipated.” The Committeewas concerned the Regulations hadresulted in “higher prices” for pharma-ceuticals, and commented that “thecourt’s are fully capable of determiningappropriate procedures [in patent dis-putes], which should not differ substan-tially from one industry to another.”

Comparable legislation in the US

Canada’s PM (NOC) Regulations areloosely modeled on the Hatch-Waxmanamendments of 1984,54 the equivalentU.S. legislative scheme.55

Unlike Canada’s PM (NOC)Regulations, the U.S. scheme rewards the

generic manufacturer that is first to chal-lenge the brand patent monopoly. Thefirst generic manufacturer to file a regu-latory submission in the U.S. challeng-ing a patent obtains a 180-day exclusivi-ty.56 This gives it a “head start” on othergeneric manufacturers so it can earnhigher returns on its product during the180-day period. The 180-day exclusivityis a recognition of the public interest inencouraging generic manufacturers tochallenge improper drug patent monop-olies as early as possible.

In 2003, the U.S. amended thescheme to permit only one automaticstay per generic submission. The amend-ments were in response to concernsraised by anti-trust authorities about theanti-competitive effect of multiple stays.

In the summer of 2002, as mentionedabove, the U.S. antitrust authority, theFederal Trade Commission (FTC),released a report57 dealing with, amongothers things, the anti-competitive effectof listing multiple patents for a singledrug in the Orange Book (equivalent tothe patent register in Canada). TheReport found multiple stays had extend-ed the patentees’ monopolies in certaindrugs improperly, an example beingparoxetine (the U.S. situation was notdissimilar to the Canadian chronologyset out above).

The FTC’s primary recommendationwas:

Recommendation 1: Permit onlyone automatic 30-month stay[equivalent to Canada’s 24 monthstay] per drug product per ANDA[generic submission] to resolveinfringement disputes over

16

patents listed in the Orange Bookprior to the filing date of thegeneric applicant’s ANDA.58

On October 21, 2002, in response tothe FTC Report, President George W.Bush proposed a new FDA regulation indraft, intended to impose a limit of oneautomatic stay per generic submission.President Bush expressed concerns aboutevergreening strategies remarkably simi-lar to concerns raised here in Canada.

When a drug patent is about toexpire, one method some compa-nies use is to file a brand newpatent based on a minor feature,such as the color of the pill bottleor a specific combination of ingre-dients unrelated to the drug’seffectiveness. In this way, thebrand name company buys timethrough repeated delays, calledautomatic stays, that freeze thestatus quo as the legal complexi-ties are sorted out. In the mean-time, the lower-cost generic drugis shut out of the market. Thesedelays have gone on, in somecases, for 37 months or 53 monthsor 65 months. This is not howCongress intended the law towork. Today, I'm taking action toclose the loopholes, to promotefair competition and to reduce thecost of prescription drugs inAmerica.59

After consultations, FDA issued a“final rule” on June 12, 2003, effectiveAugust 18, 2003. The rule limited abrand drug company to only one 30-month stay.60 It was estimated thechange would save consumers $35 bil-lion over ten years.61

The FDA Final Rule was somewhat

awkwardly drafted, so as not to step out-side the existing statutory wording ofthe 1984 Waxman-Hatch Act. The FinalRule said a generic need serve a para-graph IV certification (equivalent to aCanadian NOA) on the brand only if itwas an initial certification, or if a previ-ous certification did not result in a 30-month stay. For later patents, the gener-ic need only file a certification with theFDA, but did not have to serve it on thebrand. The effect was that the brandcompany no longer had the opportunityto obtain a second 30-month stay.

On December 8, 2003, the Presidentsigned the Medicare Prescription Drug,Improvement, and Modernization Actinto law. This omnibus bill madechanges to the Medicare system in theUS, but also included in Title XI amend-ments to the Waxman-Hatch Act tolimit the brand to one automatic stayper ANDA, retroactive to August 18,2003, the effective date of the FDA FinalRule. The FDA then revoked its FinalRule as unnecessary in light of this newstatutory language.62

Why not use the ordinary patentlitigation system for drugs?

The arguments usually put forward asto why a special patent-enforcementregime is required for pharmaceuticalsare:

a) patent litigation is lengthy, andinterlocutory injunctions are diffi-cult to get in such litigation;

b) pharmaceuticals spend many yearsin the regulatory process beforethey can get on the market, reduc-ing their period of effective exclu-

17

sivity, so quick remedies arerequired, and

c) generic companies have the benefitof the “early working” exception insection 55.2(1) of the Patent Act.

Are the remedies available in ordi-nary patent litigation sufficient forpharmaceutical patentees?

A patentee who establishes that itspatent is valid and infringed is entitledto relief under section 57 of the PatentAct, which “gives the trial judge in anaction for infringement of a patent awide discretion to make such order asthe judge sees fit.”63 Such an order willtypically grant the plaintiff damages, oran accounting of the defendant’s profits,as the patentee may elect, delivery up ofany infringing goods, a permanentinjunction until patent expiry, and courtcosts. Punitive damages may be availablein an appropriate case.64

These remedies have existed formany decades in Canada and elsewhereand it is difficult to see why they areinadequate in the pharmaceutical indus-try alone.

Are the Regulations necessarybecause interlocutory injunctions are too hard to get?

The Regulations effectively eliminatethe discretion of the court over thegranting of interlocutory relief in patentdisputes about drugs. They impose anautomatic injunction until the hearing,analogous to an interim injunction, andthen provide for an order of prohibitionat the hearing, analogous to an inter-locutory injunction, but without regard

to the normal test.

The three-part test that must normal-ly be satisfied before an interim or inter-locutory injunction is granted is well-known: the moving party must estab-lish:

1) a prima facie case on the merits,

2) that it will suffer irreparable harm ifthe injunction is not granted, and

3) that the balance of conveniencefavours the granting of the interlocuto-ry injunction. The moving party mustgive an undertaking as to damages.65

Interlocutory injunctions are rarelygranted in patent cases (nor in otherintellectual property cases, nor civil liti-gation of any kind), because the courtshave long regarded it as unfair to enjointhe defendant before trial, except inextraordinary circumstances.

However, patentees and litigants inall industries are subject to the sameconstraints in attempting to get inter-locutory relief, and are faced with thesame challenges in getting cases to trialexpeditiously. The appropriate responseto delays in getting trial dates is toincrease court resources by, for example,hiring more judges, which the FederalCourt seems to be doing.

Are the Regulations necessarybecause of long regulatory delaysfor drug approvals?

Many patentees outside the pharma-ceutical industry make a large invest-ment in research and may have a shortwindow of opportunity in which to sella new product, due to technologicaladvances by competitors (the computer

18

and electronics industries, for example).It is unclear why the pharmaceuticalindustry should be treated differentlyfrom the others. The best way to mini-mize regulatory delays would appear tobe to accelerate the drug approvalprocess.

Are the Regulations needed becauseof the "early working” exception?

The “early working” provision cre-ates an exception available to any pat-entee, in any industry. The exceptionprovides:

55.2 (1) Exception - It is not aninfringement of a patent for anyperson to make, construct, use orsell the patented invention solelyfor uses reasonably related to thedevelopment and submission ofinformation required under anylaw of Canada, a province or acountry other than Canada thatregulates the manufacture, con-struction, use or sale of any prod-uct.

The subsection of the Patent Act thatauthorizes the PM (NOC) Regulationsmakes reference to the early workingprovision:

4) Regulations - The Governor inCouncil may make such regulations as the Governor inCouncil considers necessary forpreventing the infringement of apatent by any person who makes,constructs, uses or sells a patentedinvention in accordance with sub-section (1)…

The PM (NOC) Regulations are notnecessary to determine whether theexception applies in any particular case,nor to impose remedies if not. The usualremedies for infringement can be pur-sued against a defendant in any patentaction who raises the early workingexception as a defence, and the courtcan determine at trial if the defenceapplies.

The “early working” exception hasbeen upheld by a dispute panel of theWorld Trade Organization as a reason-able “limited exception” under Article20 of the TRIPS agreement on its ownmerits, and not because the PM (NOC)Regulations exist.66 The “early working”exception in any event existed at com-mon law before the passing of subsec-tion 55.2(1) or (4).67

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ABUSIVE STRATEGIES fall under 10interrelated categories:

1. Multiple stays.2. Listing patents for non-approved

formulations and uses.3. Listing of inappropriate and irrele

vant patents.4. Late listing of patents after gener

ic submission filed.5. Employing “use” patents to pre

vent sale for non-patented uses.6. Litigation solely to trigger the

automatic stay.7. Use of the Regulations to stop

non-generic products: Biolyse case.8. Litigating NOC revoked.9. Litigating to delay payment of

damages indefinitely.10. Double jeopardy: if generic wins

NOC case, it’s still sued for patent infringement.

1. Multiple stays: Generic winsin court, but can’t get onthe market because newpatents are listed followingdismissal of prohibition pro-ceedings

Diagrams at Appendices A and Bsummarize the multi-patent strategyused by the brands for several“blockbuster” drugs. These includeparoxetine (PAXIL, for treatment ofdepression) and omeprazole(LOSEC, for treatment of ulcers).

In both cases, the automaticinjunction kept the generic versionoff the market for years after thebasic patent had expired.

Multi-patent strategies were alsoused for other best-selling drugs,including fluconazole (DIFLUCAN,an antifungal agent), diltiazem(TIAZAC, a calcium channel blockerused in treatment of cardiovasculardisease), citalopram (CELEXA, aselective serotonin re-uptakeinhibitor (SSRI) used in the treat-ment of depression) and norfloxacin(NOROXIN), an antibiotic.

The litigation for these block-buster drugs typically lasted 3-4years on average, with court pro-ceedings relating to paroxetine tak-ing 7 years, and those for diltiazemongoing since January 2001. All

20

Part IIHow the Regulations Foster Abuse

”…society would be deprivedof the benefit of new methodsof using existing pharmaceuti-cal medicines at a lower cost.”

Federal Court of Appeal ruling

involved multi-ple automaticinjunctions perdrug relating toseveral listedpatents.

Similar multi-stay strategies arebeing used in theU.S. for thesedrugs. The FTCReport usedparoxetine as akey example ofabuse.1

As indicatedby the above examples, the use ofmultiple-patent strategies to keepgeneric products off the market inCanada and the U.S. has beenemployed increasingly for block-buster drugs whose basic patentshave expired, to extend marketexclusivity as long as possible.

2. Listing patents on non-approved formulations anduses: Eli Lilly andGenpharm cases

Multiple-patent strategies recent-ly became much easier to carry out,to the point that it may become verydifficult to bring out any new gener-ic products.

In Eli Lilly v. Minister of Health,2

the Federal Court of Appeal decidedby a 2 to 1 margin (with a strong dis-sent) that patents on non-approvedformulations can be listed on thepatent register. Previous case law3

had upheld theMinister in refus-ing to list suchpatents; a patentcould only belisted if itclaimed the ver-sion of a drug forwhich the pat-entee had mar-keting approvalfrom HealthCanada.

A “formula-tion patent” is apatent on the

active ingredient in combinationwith various fillers or coatings, orformulated into a dosage form in acertain way. Such patents are usuallygranted long after the active ingredi-ent is too old to be patentable on itsown.

The Lilly decision on non-approved formulations was recentlyextended by the Federal Court tonon-approved uses in Genpharm v.Canada.4

The result of these cases is that apatent on a non-approved formula-tion or use can now be listed by abrand for a drug. It is unlikely a gener-ic would infringe such patents sincethey do not apply even to the brand’sown drug. An endless succession ofsuch patents can be listed, and used tore-start the automatic stay.

3. Listing of inappropriate andirrelevant patents throughsupplemental submissions, etc.

21

”Nothing drug companies do isas profitable as stretching outmonopoly rights on theirblockbusters. Extending thatprivileged time by a variety ofstratagems is the most innova-tive activity of big pharma. Forblockbuster drugs, it is certain-ly the most lucrative."

Former editor-in-chief of the New England Journal of Medicine Dr. Marcia Angell in her book The Truth About Drug Companiespage 173-174.

Brands litigate continually to listas many patents as possible. Theeffect is that there are now no effec-tive limits on listing patents sequen-tially over time, in order to re-startthe automatic stay. Neither the 1998amendments nor efforts by HealthCanada to police the register preventnew patents from being listed. Thefollowing is a summary of strategiesused by the brands to list as manypatents as possible on the patentregister.

Patents filed with a supplemen-tal submission, but not relevant tothe supplemental submission:Brand-name companies can listpatents with minor supplementarynew drug submissions (SNDS) whichmerely amend the brand’s drugapproval information filed withHealth Canada, even if the patent isunrelated to the amendment. Forexample, the Court of Appeal recent-ly held that Abbott Laboratoriescould list a patent on a formulationof clarithromycin, an antibiotic,with even a minor “supplemental”submission dealing with an unrelat-ed addition to the approved labelinginformation for its clarithromycinproduct BIAXIN BID.5

This opened the floodgates.Abbott has now added eight morepatents to the register for BIAXINBID.

Product Name Change:Patentees have even attempted tolist patents with submissions formere changes in the name of theproduct. Brand company Ferring

listed patent ‘296 for desmopressinacetate (CONCENTRAID, for dehy-dration and other symptoms). Thepatent was out of time to be listedunder the Regulations. However,Ferring was able to list it anyway byfiling a supplemental submission fora change to the product name. Thisfiling restarted the time limit, saidthe lower court. The Federal Courtof Appeal overturned,6 holding thatthe name change was clearly part ofa strategy designed to overcome thetime limitation.

Manufacturer Name Change:Patent ‘436 was submitted forsevoflurane (SEVORANE, a generalanesthetic) with annual sales of $12million, in connection with a sup-plemental change seeking a changein the manufacturer’s name. Thecourt upheld the Minister in refus-ing to list this patent.7 Brand giantAstraZeneca recently tried the samestrategy with its blockbuster ulcerdrug omeprazole.8

Priority date v. “filing date”: Inorder to be eligible for listing, the fil-ing date of a patent must be prior tothe submission date. Brand compa-nies sued the Minister of Healthasserting the “filing date” means thepatent priority date, usually approx-imately a year earlier. This wouldgreatly expand the class of patentsthat can be listed.

This argument was rejected bythe courts.9 Among the patents atissue was one for azithromycin(ZITHROMAX, an antibiotic).However, even though the court

22

held the patent was out of time to belisted, the azithromycin patent wasthen listed with a later supplemen-tary submission, and used to triggerautomatic injunctions against sever-al generic companies.10 This showsthe time limit for listing a patentunder the Regulations is meaningless.

Listing patents for non-market-ed products: Brand-name drug com-panies remove products from themarket as their patent expiry drawsnear and replace them with slightlydifferent dosage forms, againstwhich more patents can be listed.

For example, omeprazole cap-sules were removed from the marketby AstraZeneca in 1996 and replacedwith tablets. The change did notbenefit patients in any way. In 2000AstraZeneca listed an additionalpatent (‘762) for the capsules11 (atleast four were already listed) andthe courts held that generics mustaddress the patent.

AstraZeneca listed still otherpatents for omeprazole capsules thatwere not even applied for until yearsafter its capsules were removed fromthe market in 1996. AstraZenecaargued such patents can be used torevoke an NOC issued by HealthCanada to a generic firm in Canada,although generic versions ofomeprazole were already on themarket in the U.S. and Europe. Thecourts dismissed the argument, not-ing that there had already been 11years of litigation over omeprazolebetween the generic and brandunder the Regulations.12

4. Late listing of patents:Patent listed after genericfiles its submission

Brand-name drug companiesoften list “later issued” patents aftera generic submission has been sub-mitted to Health Canada. For clar-ithromycin, Abbott Laboratories list-ed a patent (‘732) on the register inFebruary 2002, even though itsproduct had been on the marketsince 1992. Various generic submis-sions for clarithromycin had alreadybeen submitted to Health Canada bygeneric manufacturers before thepatent was listed. Generic manufac-turers had to serve NOAs, triggeringthe 24-month stay.

Although the generics’ submis-sions compared their versions of thedrug with what Abbott Laboratorieshad been selling since 1992 (tech-nology that existed before the ‘732patent application was even filed),they were nevertheless subject to theautomatic stay resulting from serv-ing NOAs to the ‘732 patent. Abbottthen listed 8 more patents between2002 and 2004, triggering furtherautomatic stays.

Patents have been listed in thismanner right up to one day prior tothe hearing of prohibition proceed-ings13 where the generic has com-pleted its Health Canada approvalprocess, and has won all of the pro-hibition cases up to that point (asfor diltiazem in Biovail) or was onthe eve of a hearing on the onlypatent listed to that point (as forcitalopram in Genpharm).

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5. ‘Use’ patents

Brand-name drug companies cansometimes extend their marketmonopoly after expiry of the basicpatent by obtaining patents claim-ing the use of the drug in treatmentof allegedly new diseases.

Even if the generic states it willnot seek approval for the patenteduse, the brand company can use theRegulations to prevent the genericmanufacturer from receivingapproval for its drug so that it can-not be sold, even for non-patenteduses.14 Use patents have been heldinvalid15 yet still trigger the automat-ic stay until the hearing.

Recent cases involving a usepatent for omeprazole highlight theunpredictable nature of litigationabout use patents under theRegulations. In one case16 the courtrejected the brand company’s sub-mission that a generic manufacturershould be prohibited unless it canprove that no one in the worldwould ever use the generic drug forthe patented use. However, inanother case involving omepra-zole,17 the court granted prohibitioneven though the case involved thesame drug and patent.

In the former case, the FederalCourt of Appeal commented:

“Thus Apotex cannot be preventedfrom obtaining an NOC solely on thebasis that it will sell omeprazole. If itwere otherwise, then serious policyissues would arise. If there was any like-lihood that a patient would consume ageneric product for a patented use, thenthe generic product would not be

approved. This would prevent new usesfrom being approved for existing drugsbecause there is always the possibilitythat someone somewhere will use thedrug for the prohibited, patented pur-pose. This would result in a real injus-tice: since a generic company cannotpossibly control how everyone in theworld uses its product, the preventionof the generic from marketing the prod-uct would further fortify and artificiallyextend the monopoly held by thepatent holders. The patent holderwould, therefore, effectively controlnot just the new uses for the old com-pound, but the compound itself, eventhough the compound itself is not pro-tected by the patent in the first place.The patent holders, as a result, wouldobtain a benefit they were not meant tohave. In the end, society would bedeprived of the benefit of new methodsof using existing pharmaceutical medi-cines at a lower cost.”18

Yet if use patents are listed, theautomatic 24-month stay is never-theless in effect, at least until thehearing.

6. Delays/Abuses of litigationprocess solely to triggerautomatic stay

Brand-name drug company pat-entees frequently start cases under theRegulations, even when there is clearlyno real patent issue, solely in order toobtain the stay. Some examples:

Cefuroxime: The brand name ofthis drug is CEFTIN, an antibioticwith annual sales of $11 million.GlaxoSmithKline lost a court caseunder the Regulations.19 Generic drugcompany Apotex then made a

24

minor variation to its submission,and had to file a new notice of alle-gation. Although all the patentissues had been litigated in the pre-vious proceeding, GSK still com-menced a proceeding, raising thesame issues. It is clear that it did sosolely to trigger the automatic stayand block the generic from comingto market. The case was eventuallystruck out as an abuse of process.20

Lovastatin: MEVACOR is a lipid-lowering agent with annual sales of$98 million. Generic versions of thisblockbuster cholesterol drug werekept off the market for many yearsby litigation under the Regulations.The proceedings were eventuallydismissed long after Health Canada’shealth and safety approval processfor the generic products was com-plete. For example, one prohibitioncase kept Apotex’s generic productoff the market for years but brandcompany Merck Frosst never evenasserted in the proceeding that itspatent was in fact infringed.

Simvastatin: ZOCOR, a lipid-lowering agent with annual sales of$267 million. Merck Frosst obtaineda stay by commencing litigation butnever argued that the patent was infact infringed. Apotex served its alle-gation of non-infringement prior toserving its submission, as it was per-mitted to do under the pre-1998Regulations. When the case got to ahearing more than two years later,Merck Frosst did not argue that thepatent was infringed, but thatApotex’s allegation was “premature”

and not allowed under the post-1998amendments.21 Apotex served a newnotice of allegation. Merck Frosststarted new prohibition proceedings,but again did not even argue itspatent was infringed. Merck’s secondcase was also dismissed.22

7. Preventing market entry of non-generic products: The Biolyse case

The Regulations are now appliedby the Minister to impose an auto-matic stay even against brand com-panies. For example, Bristol-MyersSquibb used the Regulations to havean NOC revoked after it was issuedto Biolyse, a small company that hadapproval to sell a low-cost version ofpaclitaxel (TAXOL), a cancer drug.

Biolyse’s product was approvedbased on its own clinical trial.However BMS sued Health Canadaand Biolyse saying the NOC shouldnot even have been issued, basing itsargument on a poorly worded amend-ment (s. 5(1.1)), passed in 1999. TheCourt found Biolyse should haveserved a notice of allegation on BMSand ordered the NOC revoked.23

8. Litigating NOC revoked

A new strategy of brand compa-nies is to attack the NOC issued byHealth Canada to the generic prod-uct on the grounds that patents list-ed on the register were notaddressed.

AstraZeneca recently went tocourt to argue unsuccessfully that anNOC issued to Apotex’s omeprazole

25

capsule should be revoked, becauseof Apotex’s alleged failure to addresscertain evergreening patents listedyears after AstraZeneca removed itsown capsules from the market.24 Thecourt noted that there had alreadybeen 11 years of litigation beforeApotex obtained its NOC.

GlaxoSmithKline attempted toargue in the courts recently thatApotex’s NOC for CFC-free salbuta-mol, an asthma drug, should berevoked due to Apotex’s alleged failureto address patents listed for its salbuta-mol product VENTOLIN, althoughApotex’s version was not based on theGlaxoSmithKline product.25

Bristol-Myers Squibb was success-ful in arguing that an NOC issued toBiolyse should be revoked, due toalleged failure to address BMS’s list-ed patents, as discussed above. Thisissue was heard by the SupremeCourt of Canada in November 2004.

9. Delayed payment of dam-ages: s. 8 cases

Section 8, added in the 1998amendments to the Regulations,states that the brand company maybe liable to the generic manufactur-er for damages suffered as a result ofthe delay in obtaining an NOC dueto the Regulations.

Brand-name drug companieshave vigorously opposed any s. 8cases, and claim the damages sectionitself is unconstitutional. Brand com-panies typically bring many motionsto delay cases proceeding to trial,

including motions for summary dis-missal, removal of the brand compa-nies’ corporate parents as parties,amending statements of defence andcounterclaims, particulars, com-pelling attendance of witnesses,striking portions of damages andextensions of time. As of June 2004,there were 13 s. 8 cases proceeding totrial, five of which were started as farback as 2001, but it will years beforeany of these cases get to trial.

As the Commissioner ofCompetition pointed out onFebruary 27, 2004, Canadian citi-zens and governments are not enti-tled to damages under s. 8. Thus thepeople of Canada will never receivecompensation, even though theypaid more for drugs due to theimproper monopoly during thedelay. The table on the facing pagesets out drugs that were delayedfrom reaching the market and arecurrently the subject of s. 8 proceed-ings.

Many other major drugs are stillcaught up in litigation under theRegulations, and delays may contin-ue for years due to the relative easewith which the automatic stay canbe restarted. Section 8 cases seekingdamages can only be commencedonce an NOC is issued to the gener-ic product.

26

27

Generic Name Brand Name Indication/ Regulatory Date of Annual Sales (000s)Treatment Process Notice of in final year prior to

Complete Compliance first generic entryFrom Health Canada (Source: IMS HEALTH)

Acyclovir ZOVIRAX Antiviral 15/02/96 21/08/97 $22 (1996)Cetirizine ZYRTEC Allergies 15/06/97 21/10/98 $586 (1997)Citalopram CELEXA Depression 24/07/02 04/01/04 $153,918 (2003)Fluconazole DIFLUCAN Antifungal 08/12/93 09/10/98 $14,107 (1997)Lovastatin MEVACOR Cholesterol-lowering 26/04/96 26/03/97 $94,941 (1996)Nizatidine AXID Ulcer 30/04/96 30/04/97 $14,518 (1996)Norfloxacin NOROXIN Antibiotic 31/05/93 16/07/98 $17,202 (1997)Naproxen SR NAPROSYN SR Anti-inflammatory 04/07/95 04/05/99 $2,182 (1998)Omeprazole LOSEC Ulcer 04/01/02 27/01/04 $411,880 (2003)Paroxetine PAXIL Depression 05/10/99 23/10/03 $227,517 (2002)Terbinafine LAMISIL Antifungal 28/03/99 16/05/00 $25,693 (1999)

10. Double jeopardy: if genericwins NOC case, it can stillbe sued for infringement ofthe same patent

The generic faces double jeopardyunder the Regulations. Even if it“wins” litigation under theRegulations and gets its product onthe market, it can still be sued againon the same patents it has alreadyspent years litigating. This is becauselitigation under the Regulations doesnot result in a final determinationby the court whether the patent inquestion is valid or infringed.

The Regulations in other wordslead to complex and expensive litiga-tion which does not resolve the issuein dispute between the parties: is thepatent valid and infringed or not?

There are several instances wheregenerics have spent years in litiga-tion under the Regulations in orderto get their product on the market,only to be sued again and face fur-ther litigation once the productenters the market. AstraZenecarecently sued Apotex in respect ofomeprazole capsules when theyfinally went on the market aftereleven years of litigation under theRegulations.26 Other generic productson the market now involved inpatent litigation, which were alsolitigated under the Regulations,include lisinopril,27 nizatidine,28 andlovastatin.29

ConclusionAll of this must be weighed against the cost of the Patented

Medicines (Notice of Compliance) Regulations to Canadian society.Brand-name drug companies’ evergreening strategies under theRegulations have an obvious downside: non-infringing lower-costgeneric products are inevitably kept off the market.

This raises drug costs for Canadian governments, employers andconsumers. It also creates an economic disincentive to the challeng-ing of potentially invalid patents, although such challenges have thepotential to benefit the public at large, and are indeed essential if thepatent system is to function as intended.

Conversely, the Regulations create an obvious incentive to litigateweak patent claims, and engage in practices designed to re-start theautomatic 24-month stay and extend the monopoly indefinitely. Asmentioned earlier, an unfortunate result of the Regulations is thatbrand-name drug companies now find it more lucrative to litigatethan to innovate.

As well, the issue between the parties (is the patent valid andinfringed?) is not, and cannot be, determined under the Regulations,defeating the normal purpose of the courts: to resolve civil disputes.

Anecdotal evidence suggests the sheer volume of pharmaceuticaljudicial review applications have led to long delays in getting trialdates for non-pharmaceutical cases. This unfortunate result is alsoclearly not in the broader public interest.

In short, brand-name drug companies should not be given auto-matic extensions of their market monopolies simply because theydecide to sue a generic pharmaceutical manufacturer.

The normal litigation process should be used to resolve patent dis-putes in the pharmaceutical industry, as in all other industries inCanada.

The courts can then determine what interlocutory relief or otherprocedural measures are appropriate in any given case, and deter-mine the patent issues at trial.

Patentees would still be entitled to 20 years protection of theirpatents, and could still enforce their patents in the courts, andCanada would still be in compliance with its international obligations.

28

FootnotesPART I

1. SOR/93-1332. SOR/98-166. The amendments included the

following: the 30-month stay became 24months, the damages section was amended(section 8), the right to serve a notice of alle-gation of non-infringement prior to filing theANDS was removed, the Minister’s authorityto audit the patent register was confirmed,an early dismissal section was added (6(5)),disclosure of relevant portions of second-per-son submission was provided for (6(7)), andsection 4 was amended, possibly with theintent of limiting to some extent the patentsthat can be listed on the register.

3. SOR/DORS/99-379. The effect of theseamendments was to add s. 5(1.1), the intentof which seems to have been to ensure thatthe regulations applied even if the genericsubmission compared itself to an existinggeneric product. Section 5(1.1) has beenheld to bring a non-abbreviated submissionbased on clinical trials within the scope ofthe Regulations: Bristol-Myers v. Biolyse, 2003FCA 180, leave to appeal to Supreme Courtof Canada granted, November 20, 2003,SCC No. 29823.

4. Merck Frosst v. Canada (Minister of NationalHealth and Welfare), (1998), 80 C.P.R. (3d)368 (S.C.C.) at 384, para. 32, 33.

5. PM(NOC) Regulations, s. 3, 4.6. PM(NOC) Regulations, s. 5(1)(a).7. PM(NOC) Regulations, s. 5(1)(b).8. PM(NOC) Regulations, s. 5(3)(a).9. PM(NOC) Regulations, s. 6(1).

10. PM(NOC) Regulations, s. 7. If litigation wascommenced prior to March 12, 1998, theautomatic stay is 30 months as in Hatch-Waxman.

11. PM(NOC) Regulations, s. 7.12. Bayer A.G. v. Canada (Minister of National

Health and Welfare) (1993), 163 N.R. 183 at189-90, 51 C.P.R. (3d) 129 (F.C.A.).

13. PM(NOC) Regulations, s. 6(1).14. Eli Lilly & Co. et al. v. Apotex Inc. et al. (1997),

76 C.P.R. (3d) 1 (F.C.A.) at 5 - 6.15. Merck Frosst v. Minister of National Health &

Welfare (1994), 55 C.P.R. (3d) 302 at 319(F.C.A.).

16. Pharmacia Inc. v. Canada (Minister of NationalHealth and Welfare)(1994), 58 C.P.R. (3d)209 (F.C.A.) at 217.

17. Merck, supra. at 320.18. After being prohibited in several NOC cases

with respect to naproxen SR, Apotexobtained a declaration that the patent wasnot infringed and invalid at trial, Apotex v.Hoffmann La Roche, F.C.T.D. Court File no. T-2870-96, Reasons, April 23, 1999. The pro-hibition order granted years earlier was setaside, Hoffman La Roche Limited v. Apotex Inc.File no. T-1898-93, April 30, 1999, but onlyafter the generic NOC had been delayed foryears.

19. The damages section, section 8, was amend-ed in 1998. There are now several cases on-going seeking damages, but none have yetreached trial.

20. PM(NOC) Regulations, s. 5(2).21. SmithKline Beecham v. Apotex (1999) 1 C.P.R.

(4th) 99, affirmed (2001) 10 C.P.R. (4th) 338(F.C.A.).

22. SmithKline Beecham v. Apotex (2001) 14C.P.R. (4th) 76, affirmed (2002) 21 C.P.R.(4th) 129 (F.C.A.).

23. GlaxoSmithKline v. Apotex 2003 FCT 687. 24. A motion to have this case dismissed on the

grounds the patents were not eligible for list-ing was dismissed; GlaxoSmithKline v. Apotex2003 FC 1055.

25. GlaxoSmithKline v. Genpharm 2003 FC 1248.26. 2003 FCT 687, paragraph 88.27. Generic Drug Entry Prior to Patent

Expiration, an FTC Study, Federal TradeCommission, July, 2002, p. viii.

28. Deprenyl v. Apotex (1995), 60 C.P.R. (3d)501(F.C.A.), Eli Lilly v. Apotex (1996) 68 C.P.R.(3d) 126 (F.C.A.).

29. Merck v. Minister of Health (2001), 12 C.P.R.(4th) 383.

30. Glaxo Group Ltd. v. Novopharm Ltd. (1999),87 C.P.R. (3d) 525 (F.C.A.), Novartis v.Minister of Health 2003 FCA 299, Procter &Gamble v. Genpharm 2004 FC 204.

29

31. Hoffman-La Roche Ltd. v. Canada (Minister ofNational Health and Welfare)(1995), 62 C.P.R.(3d) 58 at 72, aff’d (1995), 67 C.P.R. (3d)25, leave to appeal to SCC dismissed, (1996)3 S.C.R. xi.

32. Warner Lambert v. M. of H. (2001) F.C.J. No.801, Eli Lilly v. M. of H., T-1212-00, January10, 2002.

33. Eli Lilly v. Minister of Health, 2003 FCA 2434. Genpharm v. M.O.H. 2003 FC 1148.35. Food and Drug Regulations. C.08.003.36. Apotex v. Minister of Health (1999), 87 C.P.R.

(3d) 271, affirmed (2001) 11 C.P.R. (4th)538.

37. Bristol Myers Squibb v. Canada (A.G.) 2002FCA 32.

38. Ferring v. Apotex 2003 FCT 293.39. 2003 FCA 274.40. Hoffmann-LaRoche v. Minister of Health 2004

FC 1547.41. Abbott, 2004 FCA 154.42. The latest patent was listed in August, 2004.43. Patented Medicines (Notice of Compliance)

Regulations (Reference), (2003), 22 C.P.R.(4th) 62.

44. Under section 28.1 of the Patent Act, apatent application filed in Canada can claimpriority to the date of a patent applicationfor the same subject matter filed in anothercountry up to a year earlier, commonlyknown as the “priority date.” The prioritydate is the key date when assessing whetherthe patent my be invalid because the inven-tion was already known.

45. Pfizer, Schering v. Canada 2002 FCT 706,affirmed 2003 FCA 138, leave to appealto SCC refused, [2003] S.C.C.A. No. 224.

46. Listed patents need not be addressed, how-ever, if the first person’s product was with-drawn from the market before the patentswere listed. AstraZeneca v. Minister of Healthet al. 2004 FC 1277.

47. On-line at http://patents1.ic.gc.ca/srch_sim-e.html.

48. Health Canada’s Annual Drug SubmissionPerformance Report, 2003, p. 36. Online athttp://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/tpd_annual03_e.pdf, last visited October 1, 2004.

49. Therapeutic Products Directorate StatisticalReport 2003, page 7. On-line athttp://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/patent_statistical_report_2003_e.html,last visited October 1, 2004.

50. Romanow Commission: “Building on Values;the Future of Health Care in Canada,” p. 208.

51. Romanow Report, p. 208 - 209.52. Summary of evidence and submissions,

Patented Medicines (Notice of Compliance)Regulations, Parliamentary Research Branch,28 August 2003.

53. Letter from Sheridan Scott, Commissioner ofCompetition to Tim Gilbert, February 27,2004.

54. Drug Price Competition and Patent TermRestoration Act, 1984, Public Law 98-417[S.1538]; September 24, 1984, known as theHatch-Waxman Act After the sponsors of thebill, Representative Henry Waxman, andSenator Orrin Hatch.

55. See Hore, E. “A Comparison of United Statesand Canadian Laws as They Affect GenericPharmaceutical Entry,” 55 Food and DrugLaw Journal 2 2000 at 373.

56. Food, Drug and Cosmetic Act, Section 505(j)(D).

57. Generic Drug Entry Prior to Patent Expiration:An FTC Study, Federal Trade Commission, July,2002.

58. FTC Report p. ii.59. Remarks by the President on Prescription

Drugs, The Rose Garden, October 21, 2002.Seehttp://www.whitehouse.gov/news/releas-es/2002/10/20021021-2.html

60. Federal Register, June 18 2003 (68 FR 36676).61. Statement of FDA counsel Daniel Troy to the

Committee on the Judiciary, US Senate,August 1, 2003.

62. Federal Register, March 10, 2004 (69 FR11309).

63. Bayer AG et al. v. Apotex Inc. (2002), 16C.P.R. (4th) 417 (Ont. C.A.) at paragraph 11.

64. Lubrizol Corp. v. Imperial Oil Ltd. (1996) 67C.P.R. (3d) 1 (FCA). Apotex v. Merck (2002),19 C.P.R. (4th) 460.

30

65. RJR-Macdonald Inc. v. Canada, [1994] 1 S.C.R. 311.

66. Canada - Patent Protection of PharmaceuticalProducts, WT/DS/114 (March 17, 2000).

67. Micro Chemicals Ltd. v. Smith Kline & FrenchInter-m. Corp. [1972] S.C.R. 506, 520.

PART II1. See for example, FTC Report, p. 48-49,

which describes the multi-patent strategyused in the U.S. for paroxetine.

2. Eli Lilly v. Minister of Health 2003 FCA 24.3. Such as Warner-Lambert v. Minister of Health

2001 FCT 514.4. Genpharm v. Canada (Minister of Health)

2003 FC 1148.5. Abbott Labs v. Apotex 2004 FCA 154; Abbott

Labs v. Pharmascience 2004 FCA 154; AbbottLabs v. ratiopharm 2004 FCA 154.

6. Apotex Inc. v. Ferring and AG Canada 2003FCA 274. A similar strategy was attemptedin AstraZeneca v. M.O.H., 2004 FC 736.

7. Toba Pharma Inc. v. A.G. Canada, 2002 FCT927.

8. AstraZeneca v. AG Canada 2004 FC 736.9. Schering v. AG Canada 2002 FCT 706; Appeal

dismissed March 14, 2003; leave to SCCdenied Nov. 27, 2003.

10. The ‘071 patent, listed August 2003 wasused by Pfizer to start automatic injunctionsagainst four different generics in 2003 and2004.

11. Apotex v. M.O.H., Astra Zeneca 2004 FC 650.12. AstraZeneca v. Apotex, Minister of Health 2004

FC 1277.13. Genpharm v. Canada (Minister of Health)

2003 FC 1148; Biovail v. Minister of Healthand Rhoxalpharma 2004 FC 257.

14. P&G v. Genpharm (2002 FCA 290), AB Hasslev. Rhoxalpharma (2002 FCT 780) wheregeneric drugs were prohibited because ofmethod of use patents although generics didnot seek approval for such use. In contrast,the court dismissed against a generic manu-facturer that did not seek approval forpatented use: AB Hassle v. Apotex 2002 FCA421; leave to SCC denied March 23, 2003.

Similarly, in AB Hassle v. Genpharm 2003 FC1443 generic omeprazole was prohibited,yet prohibition actions against a secondgeneric were dismissed on same drug andsame patents: AB Hassle v. Apotex 2004 FC379; Hassle v. Apotex 2004 FC 71; AB Hasslev. Canada 2001 FC 1264; 2002 FCA 421.

15. Pfizer v. Apotex 2002 FCT 1138.16. AB Hassle v. Apotex Inc. 2002 FCA 221.17. AB Hassle v. Genpharm 2003 FC 1443.18. AB Hassle v. Apotex Inc. 2002 FCA 221, para-

graph 57.19. Glaxo v. Apotex T-415-98, aff’d 2001 FCA 96.20. Glaxo v. Apotex 2001 FCT 16.21. Merck v. Apotex T-418-98, May 3, 2000.22. Merck v. Apotex 2002 FCT 1195.23. BMS v. Biolyse Pharma and A.G. Canada 2003

FCA 180; leave to appeal to SCC grantedNov 20, 2003.

24. AstraZeneca v. Apotex, Minister of Health,2004 FC 1278 and 1277.

25. GlaxoSmithKline v. MOH, Apotex, 2004 FC1302.

26. AstraZeneca v. Apotex, T-1409-04.27. Merck v. Apotex, T-2792-96.28. Eli Lilly v. Apotex, T-1100-97.29. Merck v. Apotex, T-1272-97.Timeline (Aug

1998 - May 2004).

31

32

^ 1999 ^ ^ ^ 2000 ^ ^ ^ 2001 ^ ^ ^ 2002 ^ ^ ^ 2003 ^ ^ ^ 2004 ^ ^ ^

Automatic Stay(T-1914-01) Prohibition GrantedRe: ’751 patent June 20, 03Oct 24, 01 Appeal Dismissed

Nov 1/04

Automatic Stay(T-148-02) DismissedRe: '794 patent Jan 14, 04Jan 31, 02 Appealed

Automatic Stay(T-470-02) DismissedRe: ’668, ‘762 patents Mar 16, 04Mar 19, 02 Appealed

Automatic Stay(T-660-02) DismissedRe: ’377 patent Apr 29, 04Apr 23, 02 Appealed

Automatic Stay(T-1878-02) To be heardRe: ’693, ‘891, ‘483 patents Dec 14, 04Nov 8, 02

Automatic Stay(T-766-03) To be heardRe: ’037 patent Feb 14/05May 13, 03

APPENDIX AUse of Automatic Stay Under NOC RegulationsTo Keep Apotex’s Generic Product Off Market:

Omeprazole Tablets (LOSEC)

‘483

*‘7

51‘7

94

‘762

‘647

‘693

‘891

‘377

‘668

‘037

‘537

'158 basic patent expires Aug 1, 01 Feb 3, 03 Apr 22, 04July 6, 99

*Exact date added to Register not listed on Form IV

Timeline (Aug 1998 - May 2004)Patents Listed (n=11)

NotesWhile the basic patent on omeprazole expired way back in 1999, machinations of theNOC Regulations allowed a continuing monopoly. For example:

1. There have been multiple automatic stays.2. Multiple patents (11) listed.3. Cases on tablets are still ongoing.4. Delays have extended more than 4 years after expiry of basic patent.

Action T-2146-03 seeks declaration of invalidity,which would end prohibition order, but no NOCcan be granted until case is decided.

33

^ 1999 ^ ^ ^ 2000 ^ ^ ^ 2001 ^ ^ ^ 2002 ^ ^ ^ 2003 ^ ^ ^ 2004 ^ ^ ^

Automatic Stay(T-2026-99) DismissedRe: '377 patent Sept 8, 00Nov 19, 99 Appeal Dismissed

Jun 27, 01

Automatic Stay(T-2016-99) DismissedRe: '668 patent Nov 16, 01Nov 18, 99 Appeal Dismissed

Nov 1, 02

Automatic Stay(T-2311-01) Dismissed Re: '762 patent Dec 30, 2003Dec 31, 01

APPENDIX BUse of Automatic Stay Under NOC RegulationsTo Keep Apotex’s Generic Product Off Market:

Omeprazole Capsules (LOSEC)

‘762

‘377

‘693

‘891

‘470

‘668

‘037

‘535

'158 basic patent expires Apotex completes Apotex receivesJul 6, 99 Health and Safety NOC on capsules

Review Jan 4, 02 Jan 27, 04

*Exact date added to Register not listed on Form IV

Timeline (June 1999 - May 2004)Patents Listed (n=8)

Notes1. Multiple automatic stays.2. Listed many patents around time of first dismissal.3. Patentee applied to court to have Apotex NOC quashed in

three court proceedings, all commenced in February 2004.

34

93 ^ ^ ^ 1994 ^ ^ ^ 1995 ^ ^ ^ 1996 ^ ^ ^ 1997 ^ ^ ^ 1998 ^ ^ ^

Appeal FCA

DismissedMay 8, 96

Appeal SCC

AllowedJuly 9, 98

APPENDIX CUse of Automatic Stay Under NOC RegulationsTo Keep Apotex’s Generic Product Off Market:

Norfloxacin Tablets (NOROXIN)

‘599April 8, 93

Apotex completes Health & Safety Review ApotexMay 31, 93 NOC Issued July 16, 98

Timeline (April 1993 - July 1998)Patents Listed (n=1)

Notes 1. Delay is 5.1 years.2. Shows that only one patent on the list can cause long delays.

Notes 1. Biovail guilty of misleading the US FDA in listing parallel patents in the Orange Book.2. Here, listed ‘224 one day before hearing of first prohibition proceeding.

Automatic Stay(T-1306-93) Prohibition Granted Re: ‘961 patent Dec 20, 95May 31, 93

^ 1999 ^ ^ ^ 2000 ^ ^ ^ 2001 ^ ^ ^ 2002 ^ ^ ^ 2003 ^ ^ ^ 2004 ^ ^ ^

APPENDIX DUse of Automatic Stay Under NOC Regulations

To Keep Rhoxalpharma’s Generic Product Off Market:

Diltiazem Capsules (TIAZAC)

‘085

* (Jan 24, 04)(One day beforehearing)

‘224

*Exact date added to Register not listed on Form IV ‘224 Expires Dec 23, 2016

Timeline (Aug 1998 - June 2004)Patents Listed (n=2)

Automatic Stay(T-472-02) DismissedRe: '085 patent Feb 20, 04Mar 19, 02

Automatic Stay(T-691-04)Re:‘224 patent OngoingApr 1, 04

35

APPENDIX EUse of Automatic Stay Under NOC RegulationsTo Keep Apotex’s Generic Product Off Market:

Citalopram Tablets (CELEXA)

Notes1. Example of listing a second patent immediately before a prohibition hearing.

^ 2000 ^ ^ ^ 2001 ^ ^ ^ 2002 ^ ^ ^ 2003 ^ ^ ^ 2004 ^ ^ ^ 2005 ^ ^ ^

(Sept. 16, 03)(One month beforehearing)

Apotex Completes ApotexHealth & Safety Review NOC Issued

July 24, 02 Jan 12, 04

Timeline (July 2001 - June 2004)

Automatic Stay(T-135-02) DismissedRe: ‘386 patent Nov 12, 03Jan 28, 02

‘693

Automatic Stay(T-2083-03) DiscontinuedRe: '693 patent Dec 8, 03Nov 5, 03

Automatic Stay(T-2378-03) DiscontinuedRe: '693 patent Jan 9, 04Dec 16, 03

36

^ 1996 ^ ^ ^ 1997 ^ ^ ^ 1998 ^ ^ ^ 1999 ^ ^ ^ 2000 ^ ^ ^ 2001 ^ ^ ^ 2002 ^ ^ ^ 2003 ^ ^ ^ 2004

Automatic Stay (x2)(T-2230-97) Both cases DismissedRe: '060,’649,’340 patents April 20, 99Oct 16, 97

Appeals DismissedJan 4, 01

(T-2660-96)Re: ‘060 patentDec 4, 96

Automatic Stay(T-677-99) DismissedRe: ‘637 patent July 6, 01April 16, 99 Appeal Dismissed

May 28, 02

Automatic Stay(T-1059-01) DismissedRe: ‘575 patent May 30, 03June 15, 01

Automatic Stay(T-876-02)Re: '829,’023,’522 patentsJune 6, 02

APPENDIX FUse of Automatic Stay Under NOC RegulationsTo Keep Apotex’s Generic Product Off Market:

Paroxetine (PAXIL)

‘023

‘060

‘637

‘829

‘522

‘575

‘668

‘037

'390 patent Apotex completes Apotex receivesExpired Health and Safety Review NOC on tabletsSept, 95 Oct 5, 99 Oct 23, 03

Timeline (Sept 1995 - Dec 2003)Patents Listed (n=6)

Notes 1. Multiple automatic stays.2. Multiple patents.3. Issuance delay is 4 years.

Discontinued Oct 23, 03

Additional copies available from the Canadian Generic Pharmaceutical Association www.canadiangenerics.ca