OVERLAPPING
INTELLECTUAL
PROPERTY
RIGHTS
NEIL WILKOF
SHAMNAD BASHEER
OXTORD
UNIVERSITY PRESS
OXFORD
UNIVERSITY MESS
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CONTENTS
ListofContributors
TableofCases
TablesofLegislation
Introduction
1. NavigatingtheInterface between UtilityPatentsandCopyrights
AndrewP. Bridges
A. Hypothetical
B. Conceptual Interplays betweenUtilityPatentand Copyright Law
C. PracticalConsiderations inChoiceofProtection andEnforcement
D. Conclusion
xiii
xxv
xliii
lv
1
1.01
1.04
1.37
1.91
2. TheOverlapbetweenPatentandDesign Protection
DavidMusker
23
A. Hypothetical—theCircularBeachTowel
B. Do OverlapsMatter?
C. Patent/DesignAnti-overlapProvisions
D. SystemicCross-Links
E. Patentsand Designs—TwinsorAntonyms?
E DesignLawExclusions
G. TheCircular BeachTowelRevisited
2.01
2.07
2.30
2.36
2.48
2.98
2.136
3. PatentsandTradeSecrets
A. Hypothetical
B. Introduction
C. PreferringTradeSecrecytoPatents
D. TradeSecrecyPriortoPatenting
E. TradeSecrecyAlongside Patents
F. Conclusion
Interfaces inPlant IntellectualProperty
MarkD.Janis
A. Hypothetical
B. Conceptual Overview
C. AnalysingInterface IssuesinPlantIntellectual Property
D. Conclusion
E. Summary
57
3.01
3.04
3.06
3.58
3.78
3.82
83
4.01
4.02
4.06
4.61
4.62
Contents
5. PatentsandUtilityModels
RobertHarrison
105
A. Hypothetical
B. TheUtilityModel
C. ProtectioninGermany
D. UtilityModelsWorldwide
E. TheAustraliaInnovation System
F. AEuropean Proposal
G. Examination
H. Division/Branching
I. LevelofInventiveness
J. Conclusion
K. Summary
5.01.
5.04
5.06
5.11
5.16
5.22
5.27
5.31
5.35
5.41
5.44
6. PatentsandRegulatoryDataExclusivityforMedicinalProducts
DuncanCurleyandMarleenH.J. vandenHorst
119
A. Hypothetical
B. Introduction
C. TheEUBattleground: DataExclusivity,Patents,and
Supplementary Protection Certificates
D. Conclusion
E. Summary
7. When Copyright and TrademarkRightsOverlap
CraigS.MendeandBelindaIsaac
A. Hypothetical
B. Conceptual Overview
C. 'Reality'—HowtheInterface PlaysOut intheUKandUS
D. Conclusion
E. Summary
8. TheDesign/Copyright Overlap:IsThereaResolution?
SamRicketsonand UrnaSuthersanen
A. Hypothetical
B. TheMeaningof'Design'
C. BerneConvention
D. TheParisConvention for theProtection ofIndustrial Property
E. TRIPSAgreement
F. JurisprudentialAnalysisoftheNationaland Regional
Copyright/Design Interface
G. Efficacy ofSutGenerisDesignLaw
H. Summary
vm
6.01
6.02
6.10
6.60
6.61
137
7.01
7.03
7.39
7.91
7.95
159
8.01
8.02
8.09
8.35
8.41
8.44
8.82
8.95
Contents
9. OverlappingFormsofProtectionforDatabases
JonathanBandandBrandonButler
A. Hypothetical
B. Conflicting ModelsofDatabase Protection
C. TheEuropean Union Database Directive
D. TheUnited States
E. International Agreements
E Summary
10. MoralRightsorEconomicRights?
MiraT.SundaraRajan
A. Hypothetical
B. MoralRights:ADefinition
C. TheImportance oftheIssue:ACommon LawPerspective
on MoralRights
D. TheTheoryBehind theRights:MonismorDualism?
E. TheInternationalArena:From Dualism toRealism
F. TechnologyDissolvesBoundariesbetween Rights:TheWIPO
InternetTreaties
G. TheFuture:AUnifiedAuthorsRight?
189
9.01
9.03
9.16
9.39
9.69
9.75
209
10.01
10.02
10.07
10.22
10.44
10.50
10.63
11. Protectionof'Famous'MarksunderTrademarkLawand
PassingOff
DavidLlewelyn
A. Hypothetical
B. Introduction
C. PassingOff
D. Trademark Law
E. BacktotheHypothetical
F. Summaiy
12. OverlappingRightsinDesigns,Trademarks,andTradeDress
AlanS. NemesandAnna Carboni
A. Hypothetical
B. Introduction
C. TheUnitedStates
D. TheEuropeanUnion
E. PracticalAdviceandInsights
13. OverlapsbetweenTrademarksandGeographicalIndications
DevS. Gangjee
A. Hypothetical
B. ConceptualOverview
231
11.01
11.05
11.07
11.34
11.70
11.73
251
12.01
12.02
12.04
12.39
12.92
277
13.01
13.03
Contents
C. PracticalConsiderations:Conflicts, GenericStatus,and Choosing
betweenSystems
D. Conclusion
14. DomainNamesandTrademarks
Mark V.B. Partridge
A. Hypothetical
B. TheConceptual Framework
C. PracticalAdvice
D. Application ofTraditionalTrademarkPrinciplestoDomainNames
E. Application toHypothetical
E Summary
15. PublicityRights,TrademarkRights,andPropertyRights
SheldonW.Halpern
A. Hypothetical
B. TheRightofPublicity:ProtectingtheAssociativeValueofPersona
C. Taxonomy, Categorization, andtheAnalogicalExplosion
D. TheRightofPublicityasaRightAppurtenant: Constitutional
and IntellectualBoundariesAttenuatingPropertyRights
E. TrademarkRightsasRightsAppurtenant: PropertyRights
intheMarkItself
F. Conclusion:AFunctionalBalance
G. Summary
16. TheRelationshipbetweenTrademarkRightsandUnfairCompetitionLaw
AxelNordemannandTaraMooneyAaron
A. Hypothetical
B. Introduction
C. LegalBackground
D. SlavishImitationsunderUnfair Competition LawandTrademarkLaw
E. Consumer Deception byCreatingConfusing Similaritybetween
Trademarksand/or Products underUnfair Competition Law
andTrademarkLaw
E ComparativeAdvertising
G. Discussion andSummary
17. TheRelationshipbetweenIntellectualPropertyRightsand
CompetitionLaws
ThomasC. VinjeandAihwin vanRooijen
A. Hypothetical
B. Introduction
C. AComplementaryYetTenseRelationship
D. Internal BalancinginIntellectualPropertyRights
E. UnilateralRefusals toLicenseunder Competition Law
13.10
13.29
297
14.01
1.4.03
14.62
14.98
14.108
14.113
321
15.01
15.04
15.23
15.33
15.58
15.67
15.68
341
16.01
16.02
16.05
16.10
16.23
16.41
16.56
365
17.01
17.02
17.07
17.22
17-28
Contents
F. SpecificIssuesInvolvingStandards:PatentHold-up and
the (F)RAND Defence
G. Conclusion
H. Summary
Comparison Tables
Australia
Brazil
Canada
China
France
Germany
India
Israel
Japan
Korea
Mexico
Netherlands
Russia
Singapore
SouthAfrica
Turkey
UnitedArabEmirates
Index
17.69
17.84
17.86
387
387
395
403
411
419
427
435
443
451
459
466
474
482
490
498
505
513
521
PATENTS AND REGULATORY DATA
EXCLUSIVITY FOR MEDICINAL PRODUCTS
Duncan Curley,Solicitor, Innovate Legal,London, UKand Marken H.], van den Horst,
Attorney at law,BarentsKransNV, TheHague, TheNetherlands*
A. Hypothetical
B. Introduction
C. TheEU Battleground: Data
Exclusivity, Patents,and
Supplementary Protection Certificates
(1) Dataexclusivity
(2) Patents
6.01
6.02
6.10
6.10
6.27
(3) Supplementaryprotection certificates
(4) Overlappingprotection?
(5) Clopidogrel
(6) Galanthamine
(7) Escitalopram
D. Conclusion
E. Summary
6.28
6.33
6.39
6.44
6.51
6.60
6.61
A. Hypothetical
Followingthe synthesisofcompound Z initslaboratories in themid-1980s, BigPharmaInc. 6.01
discovered that Z had useful biological properties. It patented compound Z and subsequently carried out extensive clinical trials on a medicine containing compound Z as the
activesubstance.The medicinewasapproved for usein humans inEurope.Theclinical trials
data package for the medicine containing compound Z was the subject of a period of data
exclusivity, but this ran out long before thepatent tocompound Z expired. In the meantime,
BigPharma Inc. had discovered that Z existed in aform comprised oftwochemically similar
but structurally different isomers.When the individual isomerswereseparated, itwas found
that one was much more biologically active than the other. BigPharma filed for a separate
patent on the active isomer,which itcalled iso-Z. It also developed a new medicine containing iso-Z asthe active substance and submitted to the relevant European authority an application for a marketing authorization. The regulatory authority was content for BigPharma
to rely on much of the clinical data that ithad already obtained on the medicine containing
the original compound (Z) and granted the marketing authorization. Nevertheless, iso-Z
was treated asa new active substance, thereby attracting a further period of data exclusivity.
Whilst both patents and data exclusivity may beavailable to protect such investments in the
field of medicines, do these rights overlap and do they always offer bullet-proof protection?
1
Theauthorsgratefully acknowledgetheassistanceofAnnemiekeKooyofBarentsKransNVinthepreparation ofthis chapter.
119
Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
B. Introduction
6.02 The focus ofthischapter isanexamination ofthelawsprevailingintheEuropean Union (the
EU) which relateto dataexclusivityand patentprotection for medicinal products for human
use.Wewill describe theEuropean system for the grant ofsupplementary protection certificates(SPCs) formedicinal products,whichprovidesalinkbetween theregulatoryand patent
frameworks. We will then address the question of any overlap between data exclusivity and
patent protection (includingSPCs) and compare this to theUS position, before concluding
with three examples from the EU which illustrate the various topics discussed.
6.03 Maintenance ofexclusivityin themarket bymeans ofpatent protection hashistorically been
the way in which companies operating in sectors that depend on research and innovation
have survived and thrived. The importance of patents for the protection of new medicinal
products (both smallmoleculesand biologicals) cannot beover-stated, but thetimespent on
invention and discoverymay represent only aproportion ofthe time that itactually takes to
bring such products tomarket. In thehealthcare field, extensivepreclinicaland clinical trials
must be undertaken to demonstrate a drug product's quality, safety, and efficacy. A dossier
containing the resultsofthesetrialsisthen submitted to the relevant regulatory authority, in
order to gain governmental approval toplace thedrugproduct on the market.The authority
assesses the data for compliance with the regulatory standards in force, before considering
whether to grant a marketing authorization that would allow the new medicine to be
prescribed by physicians and used to treat illnesses.
6.04 Themailing ofactivesubstancesfor thepurposes ofregulatoryapprovalwilloften lead to the
accumulation of valuable data on their biological effects. PhRMA, the Pharmaceutical
Research and Manufacturers ofAmerica, an industry association of originator companies,
states that (on average) $1.2 billion is invested in preclinical and clinical testing of new
medicines. 2Thisisan averagefigureand clearlythecostofobtainingdataon an experimental
medicine willvary considerably.
6.05 Clinical trials areby no means restricted only to new active substances that have never been
used before in marketed drug products. Known substances may be re-examined in studies
that involve testinganewdosageregimeor that seekto discover other biological effects, such
assecond or further medical uses. For example, in the 1980s, itwas discovered that the Bisphosphonatecompound, alendronate, could be used in the treatment ofosteoporosis. 3 This
use ofalendronate waspatented in 1982 by theIstituto Gentili research laboratories in Pisa,
Italy, which were subsequently acquired by the American pharmaceutical company Merck
& Co. Inc. Following clinical trials, Merck launched an approved drug product containing
alendronate in 1993. However, patents that claim only uses of a known compound (as
opposed tocompounds perse)can beweakand maybeliabletochallenge.Merck discovered
thistoitscost in relation toalendronate in anumber ofEuropean countries.In declaring two
2
See PhRMA's website at: <http://www.phrraa.org/issues/intellectual-property> last visited 20 February
2012.
3
SeeM.Patlak,'Bone Builders:TTieDiscoveriesBehind PreventingandTreatingOsteoporosis', (2001) 15
THEFASEB JOURNAL 1677E-1677e.
120
B. Introduction
of Merck's UK alendronate 'use' patents to be invalid in 2003, Jacob, J (as he then was)
said,
I . , . hold both patents invalid. I do so with some regret. Merck have only had afew years'
exclusiveexploitation ofalendronate.Theymustsurelyhavehad tomake averyconsiderable
investment and incurred considerable riskinbringingittomarket.And mankind is better off
asaresult. But the patent system doesnot confer monopolies on thosewhodevelop obvious
orold products,even iftheyhaveneverbeen exploited.4
It is clear from the alendronate example (above) that patents cannot always guarantee a 6.06
period of market exclusivity, after regulatory approval of adrug product has been obtained.
What about the data that was derived from the clinical trials that must be provided to the
relevant regulatory authority insupport oftheproposed medicinal useoftheproduct? Some
degree of legal protection isrequired, in order to ensure that it cannot immediately be used
byothers,given thesizeofthefinancial commitment that isusuallyassociatedwith trials and
obtaining thedata.Theconcept ofdataexclusivity—aperiod oftimeafter the initial registration ofa new drug product during which only the entity that developed the data may use it
to support additional marketing authorizations—has thus evolved.
Data exclusivity is not like other intellectual property rights, such as patents or copyright. 6.07
The latter rights may be enforced privately against infringers in the courts. Data exclusivity
isbetter characterized asagovernmental or administrative obligation not to allow data that
hasbeen provided tosupport aregistration dossier for amedicine to beused bythird parties.
Article 39(3) of the Agreement on Trade-Related Aspects of Intellectual Property Rights
(TRIPS), states as follows,
Members,when requiring,asacondition ofapprovingthemarketingofpharmaceutical orof
agricultural chemical products which utilize new chemical entities,thesubmission of undisclosed testorother data,theorigination ofwhich involvesaconsiderableeffort, shall protect
suchdata againstunfair commercial use.Inaddition, Membersshallprotectsuchdata against
disclosure,exceptwherenecessarytoprotect thepublic,orunlessstepsaretakentoensure that
thedataareprotected againstunfair commercial use.
The protection of data against disclosure as mandated by TRIPS is achieved by means of 6.08
regulatory data exclusivity in thelegal frameworks governing the authorization of medicinal
products in the EU, the USA, and in many other countries.
Data exclusivity does not last in perpetuity. After aprescribed period of time (the data exclu- 6.09
sivity period), another company may seek marketing approval for a 'generic' product, by
submitting an abbreviated application for registration that relieson theoriginal data that has
already been collected and submitted by the originator company. In theUSA, adirect link is
made between the regulatory approval of generic medicines and the patent protection status
ofdrug productsin theHatch-WaxmanActof 1984('theHatch-WaxmanAct'). 5Thislink has
been said to blur the rewards available through the patent system and drug approval regulation. 6 As we shall see, in the EU, the system conferring regulatory data exclusivity and the
patent framework areeffectively distinct.Alegallinkbetween theregulatory approval process
4
GB2118042and European patent (UK) no.0998292: TevaPharmaceuticalIndustries Ltdandothers v
Istituto GentiliSpA andMerck&CoInc[2003]EWHC5(Pat).
5
TheDrugPriceCompetitionandPatentTermRestorationActof1984.
6
R. S. Eisenberg, 'The Roleof the FDA in Innovation Policy', (2007) 13 MICH TEL & TECH LAW REV
345-388.
121
Chapter 6:Patents and RegulatoryData Exclusivityfor Medicinal Products
and the patent system isestablished in themechanism for the grant ofpatent extensions for
authorized medicinal products in the EU (supplementary protection certificates), but this
link ispurelyfunctional and itdoes not produce anyambiguity about overlapping rewards.
C. TheEU Battleground: Data Exclusivity, Patents, and
Supplementary Protection Certificates
(1) Data exclusivity
6.10 Directive 2001/83/EC on the Community Code Relating to Medicinal Products for Human
Use('theDirective') 7laysdownrulesrelatingtothemarketingofmedicinalproductswithwhich
the member statesin the EU must comply.Thecoreprovision isArticle 6,which states that,
No medicinal product may be placed on the market of a Member State unless a Marketing
authorisation has been issued by the competent authorities of that Member State in accordancewith this Directive...
6.11 Thereareseveral routesthat acompanymayfollow inorder toobtain amarketing authorizationinaccordancewithArticle6:theCentralized Procedure, 8theNational Procedure (which
maybefollowed bytheMutual Recognition Procedure), 9and theDecentralized Procedure. 10
The choice depends on the type ofproduct and whether a company wishes to obtain a marketingauthorization in one,some,orallofthemember states,which in turn maydepend on
timing and strategy considerations.
6.12 An application for marketingauthorization maybemade on thebasisofone ofthe following
articles in the Directive:
• Article 8 (3):ordinary procedure
• Article 10
• 10(1): abridged procedure
• 10(3):hybrid abridged procedure
• 10(4):procedure for biosimilar products
7
The fail text of the Directive (as amended) is available at <http://www.eraa.europa.eu/pdfs/human/
pmf/2001-83-EC.pdf> lastvisited 20February2012.
8
Following the Centralized Procedure (CP) will, if all the requirements have been met, result in one
marketing authorization valid throughout the EU (in contrast to the other routes described, which result in
marketing authorizations valid in one or more member states). An application is made to the European
Medicines Agency. For certain specific typesof medicinal product (such asthose that have been made using
biotechnological methods),obtaining amarketing authorization viatheCP ismandatory.
9
ANational Procedure results in amarketing authorization for one member stateonly.The application is
filedat the national Marketing Authorization Authority in the relevant member state. In the event that the
applicant subsequently wishes to obtain marketing authorizations for the same medicinal product in other
memberstates,thenational application offers thebasisforthefirststageofthe Mutual Recognition Procedure
(MRP).The applicant mayaskfor the authorization to be recognized byoneormore other member statesby
following theMRP.Thisprocedureisdescribed inArticle28(2) ofthe Directiveand issubstantivelysimilar to
theDecentralized Procedure.
10
The Decentralized Procedure (DCP) isfollowed iftheapplicant decides,from theoutset, to obtain marketing authorizations inseveral member statesatthesametime.The procedure isdescribed inArticle 28(1)of
theDirective.Theapplicantaskstheauthorityofonememberstatetoactasaso-calledReference MemberState
(RMS).Theapplication issubmittedwith thisauthorityandtheapplicantwillindicatetheothermemberstates
in which it wishes to obtain amarketing authorization for the same medicinal product. These other member
statesarecalled theConcerned MemberStates (CMS).
122
C. TheEU Battleground: Data Exclusivity, Patents, andSPCs
• Article 10 (bis):bibliographic procedure
• Article 10 (ter):procedure for newcombinations ofactive substances
• Article 10 (quater):approved procedure (wherethedossierholder ofaprevious authorization gives permission for references to studies from this dossier).
The distinction between an ordinary procedure (Article 8(3)), an abridged procedure 6.13
(Article 10(1)), and a hybrid abridged procedure (Article 10(3)) pertains to the nature and
scopeofthe data to besubmitted (thedossier).Anapplication for amarketing authorization
must, in principle, contain all of the data asstated in Article 8(3) of the Directive, namely
(inter alia) the results of pharmacological, toxicological, and clinical trials. An application
containing all data iscalled a 'full' or 'complete' application, or full dossier.This is regardless
ofthequestion ofwhether allofthedata arein fact new.Afull application can also comprise
data that are already part of a different application dossier, for example, if the application
relates to a new formulation of a known substance, or a second medical use, or a different
dosage regime.
Asalready stated, preclinical and clinical trials areexpensive and time consuming and often 6.14
require significant investment from the originator companies. Conducting such trials also
implies extensive testing on animals and humans. One of the objectives of the European
legislation is to ensure that such trials are not repeated unnecessarily.11 Thus, under certain
defined conditions, third parties (ie, generic companies) may refrain from repeating such
studies and may refer to the results of the relevant tests in the dossier of the earlier, original
registration (the so-called spécialité).
UnderArticle 10(1) ofthe Directive, an applicant does not have to submit afull dossier, but 6.15
isallowed to refer to the data in a marketing authorization dossier for a reference medicinal
product. This option exists ifthe medicinal product for which a marketing authorization is
beingrequested isa'pure'generic(seebelow)with respectto thereference medicinal product
and if a marketing authorization was granted for the latter medicinal product at least eight
years before the application date. An application based on Article 10(1) is referred to as an
abridged application.
Article 10(2) of the Directive defines a generic medicinal product as a medicinal product 6.16
which has the same qualitative and quantitative composition in active substances and the
same pharmaceutical form as the reference medicinal product, and whose bioequivalence
with the reference medicinal product has been demonstrated by appropriate bioavailability
studies.Article 10(2)specifies thatdifferent salts,esters,ethers,isomers(including enantiomers), mixtures of isomers, complexes or derivatives ofan active substance shall be considered
to be the same substance, unless they differ significantly in properties with regard to safety
and/or efficacy.
Article 10(3) of the Directive describes the so-called 'abridged hybrid procedure'. An appli- 6.17
cation under Article 10(3) is made for a marketing authorization for a medicinal product
that does not satisfy the definition of generic medicinal product in Article 10(2) (see above)
or whose biological equivalence cannot be demonstrated by studies or where the active
substance(s), the therapeutic indication, the strength, the pharmaceutical form, or the
manner of administration are changed, compared to the reference medicine. The abridged
11
SeeRecital 10tothe Directive.
123
Chapter 6: Patentsand RegulatoryData Exclusivityfor Medicinal Products
hybrid procedure opens up the possibility of referring to data which have already been
submitted in the dossier for a reference medicinal product, but requires the submission of
additional data that serve to bridge the differences to that reference medicinal product
('bridging data'). The bridging data may consist of (for example) bioequivalence studies
and tests demonstrating the safety and efficacy of the product for which the application
is made.
6.18 Whilst the purpose ofthe abridged procedures laid down inArticle 10isto avoid unnecessary repetition of clinical trials, a balance must be found between this imperative and the
need to stimulate the originator companies to continue to invest in the development of
new medicinal products and accordingly to contribute to human health and well-being.
This balance isfound in the form ofdata exclusivity. During the period ofdata exclusivity,
only the marketing authorization holder (that conducted the pharmacological, toxicological, and clinical trials) is allowed to use the data in order to apply for a marketing
authorization and/or to use such authorization, once obtained. Thus, it is only after the
expiration of this period that third parties (such as those seeking to bring generic medicines to market) are allowed to refer to the original data in the context of the abridged
procedures.
6.19 The data exclusivity rules are contained in Article 10(1) of the Directive. In the EU, the
current data exclusivity regime is often referred to by the shorthand '8+2+1', the figures
referring to the years that have to elapse before an abridged marketing authorization can be
applied for by third parties (eightyears) and another two or threeyearsbefore the marketing
authorization can be used by those third parties to market their product. In other words,
once (after eightyears) a third partyhas applied for and subsequently obtained a marketing
authorization on the basis of an abridged procedure in Article 10, the generic medicinal
product maynot be marketed before ten yearshaveelapsed, counted from the datewhen the
marketing authorization for the reference product was granted. In some cases, this can be
increased to elevenyears, if,
duringthefirsteightyearsofthosetenyears,themarketingauthorisation holder [ofthe reference product] obtains an authorisation for one or more new therapeutic indications which,
during the scientific evaluation prior to their authorisation, are held to bring a significant
clinicalbenefit in comparison with existingtherapies.12
The '8+2+1' data exclusivity rules (outlined above) apply to those products that have been
authorized in the EU after 30 October 2005. 13
6.20 Apart from being used to support applications for marketing authorizations, the results of
clinical trialsareoften published in the scientific literature.The fact that such data are in the
public domain does not necessarily mean that they fall outside the ambit of the protection
conferred by data exclusivity. It is important to distinguish between the availability of
data in the public domain on the one hand and the exclusive right to use such data on the
12
Seethelastsub-paragraph ofArticle 10(1).
However,datasubmitted insupport ofmarketing authorizationsapplied for before thisdatecontinue to
benefit from theprevious (non-harmonized) dataexclusivity rules.Agoodsummaryoftheprevious European
data exclusivity rules may be found in R.F. Kingham and G.H. Castle, (2000) 55 FOOD AND DRUG LAW
13
JOURNAL 209-223.
124
C. TheEU Battleground: Data Exclusivity, Patents,and SPCs
other hand. The concept of data exclusivity ordinarily entails (as the word 'exclusivity'
implies) that the company that acquired the data by conducting relevant trials can, to the
exclusion ofother parties, usesuch data for thepurpose ofmarketing the medicinal product
involved. Hence, datawhich isin thepublicdomain canstillbeprotected byaperiod of data
exclusivity.Thisspecific issuearosein both theClopidogrel and theescitalopram cases,which
will be discussed further, below.
An important concept in the EU regulatory framework when discussing data exclusivity is 6.21
theglobal marketing authorization.Thisconcept isfound inArticle6(1) (second paragraph)
of the Directive:
. . . When a medicinal product has been granted an initial marketing authorisation in
accordancewith thefirstsubparagraph,anyadditionalstrengths,pharmaceuticalforms, administrationroutes, presentations as wellasany variations and extensions shall alsobegrantedan
authorisationin accordance with thefirstsubparagraph orbeincludedin the initial marketing
authorisation.Allthesemarketingauthorisationsshallbeconsidered asbelongingtothesame
globalmarketingauthorisation, inparticularfor thepurposeoftheapplication ofArticle 10(1)
(emphasisadded).
The concept of a global marketing authorization thus entails that there is a marketing 6.22
authorization with greater scope, based on the first authorization that was granted for the
original active substance in the medicinal product. In consequence, all authorizations
granted subsequently with regard to the same substance, for instance as a consequence of
variations in theactivesubstance,form part ofthesame,initial marketing authorization. The
words 'variations and extensions' in Article 6 are taken from the successivevariation regulations, the currently valid one being Commission Regulation (EC) No 1234/2008 ('the
Variation Regulation').
Variations to medicinal products areclassified in different categories,depending on thelevel 6.23
of risk to public health and the impact on the quality, safety, and efficacy of the medicinal
product concerned. Certain changes, namely thosewhich have thehighest potential impact
on the quality, safety, or efficacy of medicinal products, require acomplete scientific assessment, in the same way as for the evaluation of new marketing authorization applications.
Other changes to medicinal products do not require an extensive scientific assessment.
According to theVariation Regulation, anextension ofamarketing authorization (or simply
an 'extension') means avariation which islisted inAnnex I to theVariation Regulation and
which fulfils the conditions specified therein. Everychange listed inAnnex Iof the Variation
Regulation isthus an extension,which isalsooften calleda'line-extension'. Every authorization granted for an extension thus forms part ofthe same global marketing authorization as
the first authorized version of the active substance(s) in a medicinal product, regardless of
whether it isin the form of anew, separate marketing authorization or asan amendment to
an existing marketing authorization.
The global marketing authorization concept has special significance for the application of 6.24
Article 10 of the Directive and accordingly for the calculation of the period in which data
exclusivity can be claimed. The period of data exclusivity iscalculated as beginning on the
date that the first of all of the authorizations in the group that forms the global marketing
authorization was granted. An applicant wishing to base its application on Article 10 of the
Directive mayrefertoeachauthorization thatforms partoftheglobalmarketing authorization
125
Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
to serve as reference medicinal product in abridged (hybrid) proceedings. 14 Therefore, even
when anapplicant for amarketingauthorization basedonArticle 10(1)or 10(3)refers to the
dossierofaspecific reference medicinalproduct (whichisfor instanceanother pharmaceutical
form than thefirst authorized versionofthereferenceproduct),theperiodofdata exclusivity
willstillbecalculated byusingthedateofthegrantofthefirst,initialversion ofthat medicinal
product.
6.25 To summarize, thegrant ofamarketing authorization byaregulatoryauthority isan administrative decision that follows, once the authority hasestablished legal and scientific compliancewith allrelevant requirements.Itdoesnot explicidyincludethegrant ofdata exclusivity
as such, nor can the decision of the authority be seen as the Vesting' of a right.Whether or
not data areprotected bydataexclusivityis,in practice,something that isassessedand determined atalater moment in time,mostlywhen third parties applyfor amarketing authorization via an abridged procedure, referring to the data in the dossier of the reference product
(spécialité).15The regulatory authority in the member statewhere the application isfiledhas
to assesswhether the data can or cannot be referred to and thus to determine whether data
exclusivity (still) exists in relation to the original dossier. Given the fact that the concept of
data exclusivity is laid down inArticle 10 ofthe Directive (prescribing the requirements for
generic applications), it is clear that the issue of entitlement to data exclusivity for specific
data onlycomesintocontention when agenericcompanystartsanabridged procedure based
onArticle 10.
6.26 The ten (possibly eleven) years of data exclusivity that are now available in the EU for new
active substances offers arelativelyhigh level ofprotection, compared to equivalent regimes
elsewhere in the world. The USA offers only an initial five years of data exclusivity for conventional small molecule drug products. 16A recent paper suggests that there are benefits to
be gained from giving small molecule drugs alonger period of data protection in the USA,
14
Thisisstated inVolume2A,Chapter ISection 5.3.1oftheNotice toApplicants,which isadocument to
beused asguidance byapplicantsfor marketingauthorizations.TheNotice toApplicantssays:
Besides,Article6(1) contains the notion ofglobal marketingauthorisation asthe initial marketing
authorisation and anyadditional strengths,pharmaceutical forms,administration routesor presentations,aswellasanyvariationsandextensions.Eachproductwithin theglobalmarketingauthorisation maybechosen asthe reference product.
TheNoticetoApplicantsdetermines (onpage35)that therequirement toobserveaperiodofeightyears before
an abridged application for a marketing authorization for ageneric medicinal product can bemade does not
applyto'(line-) extensions':
. . . Even if they are authorised in accordance with the procedure for granting a new marketing
authorisation, according to Article 6(1) of Directive 2001/83/EC, when a medicinal product has
been granted an initial marketing authorisation, any extension shall beconsidered asbelonging to
the same global marketing authorisation, in particular for the purpose of the rules on data and
marketprotection.Thismeansthatforanoriginalmedicinalproduct, thestartofthedataexclusivity
periodisthedatewhenthefirstmarketingauthorisationwasgrantedintheCommunity. Extensions
donot restartorprolongthisperiod;theywillhavethesameendpointofthedataexclusivityperiod.
1s
Wesuggestthatagenericcompanyisnot 'time-barred'from objecting toaperiod ofdataexclusivityallegedlyattachingto adossier for amedicinal product, severalyearsafter thegrant ofthe marketing authorization
for the product in question. Generic companies applying for marketing authorizations under the abridged
procedure usuallydo notobject tothegrantofthe(initial) marketing authorization for thereference medicinal
product, but rather seek to contest the consequence of data exclusivity that isattached to it by the regulatory
authority.
16
Under theHatch-WaxmanAct.Applications for approval ofnewindications (for usesotherthanthe one
forwhich the drugwasoriginallyapproved) receivethreeextrayearsofdata exclusivity.
126
C. The EU Battleground: Data Exclusivity, Patents, andSPCs
in terms of spurring innovation and ultimately consumer welfare.'7 Although there has on
occasion been some suggestion that the number ofyears ofprotection for clinical trials data
in the USAshould beraised,13theseproposalshavenot gainedtraction in the US legislature.
In contrast however, biologieshave now been granted a 12yeardataexclusivityperiod in the
Patient Protection and Affordable Care Act of 2010, implemented as part of President
Obama's reforms to the US healthcare system.19
(2) Patents
Traditionally, the pharmaceutical industry has operated by synthesizing new chemical 6.27
substances in the laboratory, testing them for biological activity and patenting them. Patent
protection is usually sought at an early stage in the life of a product, often long before it is
known whether thecompound willactuallyproveuseful as an activesubstance in a marketed
drug product. This simple model served the originator companies well for many years, but
today, looming patent expirations (the so-called 'patent clifF) on a number of big-selling
products based on small molecule active ingredients and an increased intensity of competition from the manufacturers ofgenericproductsafflict manyofthecompanies thatare active
in thissector.20Inthe 1980s,smallmoleculedrugdiscoveryprogrammeswere supplemented
by rapid advances in the manipulation of biological material, leading to the patenting of
biotechnology-derived products. Today, biological products are a boon to the life sciences
sector, although the manufacturers of so-called follow-on biologies (or similar biological
products, or biosimilars) pose a threat to some of the blockbuster biopharmaceutical products, in some markets, in the near to medium term.
(3) Supplementary protection certificates
It is often—but not always—thecasein theEU thatpatentswillprotect the market exclusivity 6.28
for both small molecule-based drug products and biologicals for longer than the data exclusivityperiod, 21 byvirtue ofthe European system for thegrant ofextensions to patent rights,
which arecalled supplementary protection certificates (SPCs) in Europe. 22
SPCs sit in a classof their own (assuigenerislegal instruments) between the regulatory and 6.29
the patent systems. SPCs extend certain rights conferred by a patent after its expiry, for a
17
D.P. Goldman, D.N. Lakdawalla, J.D. Malkin, J. Romley and T. Philipson, 'The Benefits from giving
makersofconventional "smallmolecule"drugslongerexclusivityoverclinical trialsdata',(2011)30(1) HEALTH
AFFAIRS 84-90.Thearticlereportsonthe resultsofresearch funded (inpart) byINTERPAT, anassociation of
originator pharmaceutical companies.
18
Forexample,from GlaxoSmithKline,who haveproposed that newdrugsshould receive 14yearsof data
exclusivity.
19
Partofthequidproquo forthisconcession totheoriginatorcompanieswas topavethewayfor a regulatory
framework for thespeedier authorization bythe FDAoffollow-on biologies,although at the time ofwriting,
thisframework hasnot been implemented andtheEU remainswellahead ofthegame,with aregulatory pathway for biosimilars that isbeing used successfully and a number of biosimilar products already having been
launched successfully on toEU markets.
20
A good summary of the present situation in the EU is to be found in the European Commission's
Pharmaceutical Sector Inquiry—Final Report (8July 2009), available at <http://ec.europa.eu/competition/
sectors/pharmaceuticais/inquiry/staff_working_paper_partl .pdf> lastvisited 20 February 2012.
21
TheEuropeanFederationofPharmaceuticalIndustriesandAssociations(EFPIA)publication, 'Intellectual
Property and Pharmaceuticals', page 21 (June 2008), available at <http://www.efpia.eu/Content/Default.
asp?PageID=559&DocID=4901>.
22
ForanoverviewoftheEuropeansystemforthegrantofsupplementaryprotection certificates for medicinal
products, see D. Curley, 'Extending Rewards for Innovative Drug Development', (2007) INTELLECTUAL
PROPERTY INSTITUTE.
127
Chapter6:PatentsandRegulatoryDataExclusivityforMedicinalProducts
periodofuptofiveyears.23TheEuropeanregimeforthegrantofSPCsformedicinalproducts
for human and veterinary usewasfirstproposed in aEuropean Commission Explanatory
Memorandum in 1990,inresponsetopatentextension legislation intheUSAandJapan.24
Theoriginal regulationsubsequentlycameintoforceon2January 199325andwasfollowed
inFebruary 1997byasimilarregulationforplantprotection products.26
6.30 Thejurisprudence on SPCs isstill evolving, but from the Explanatory Memorandum and
thepreambletothemedicinalproductsregulation,27itseemsclearthattheoriginal purpose
ofSPCswastocompensatethosewhoobtainedpatentsfornovelandinventiveresearchand
developmentfortheperiodofdelaythatusuallyoccursbetweenthefilingofapatentapplicationandthesubsequentgrantofamarketingauthorization.Itmaynotbeuntilthelatterpoint
in time—perhaps adecadeor soafter thefilingoftheoriginalpatent application—that the
patenteeisabletostartmarketingtheproductandtoearnmoneyfrom exclusivesales ofthat
product.SPCsarethusintendedtoaddressthecuttingdownofthetwentyyearpatentmonopolythataffectsinparticularthoseinregulatedindustriesthatcannotmarketpatentedproducts
withoutfirstconductingtrialson thoseproductsandobtainingregulatoryapproval.
6.31 Acommon objectiveinboththemedicinalandplantprotection productsSPCregimesisto
provideaperiodofexclusivity(byvirtueofbothpatentandSPC)ofanoverallmaximumof
15yearsfrom thetimethataproductfirstreceivesregulatoryapproval for marketing in the
EU,28thusprovidingalinkbetweenthepatentandtherelevantregulatorysystems.
6.32 Asstated above,in thefieldofhuman medicines,thecombination ofgranted patent rights
and theprotection offered byaSPCwillusuallyprovidelongereffective market exclusivity
in the EU than theperiod ofdata exclusivity, although sometimes experimental medicines
in the cancer or CNS therapy areas mayneed tobestudied in the clinic overa protracted
periodoftime.Relevantpatentsmaytherefore haveexpired bythetimemarketing authorizationisgrantedandadrugproduct islaunched,oralternatively,theymayexpireonlyafew
yearsafter suchlaunch.Dataexclusivitymaybevitalinsuchcircumstances,inorderfor the
originator companytoearnareturn on itsfinancialinvestmentinthe product.
(4) Overlappingprotection?
6.33 Forthemanufacturers ofgenericmedicines,animportantone-offrevenuegeneratingopportunityistobederivedbybeingthefirsttogainmarketingapprovalandlaunchagenericdrug
product on to themarket. Data exclusivity, patents,and SPCs preserve incentives for the
23
Nowextendablebyafurther sixmonths,subject to thesatisfactory completion ofapproved clinical studiesin thepaediatric population, byvirtue ofRegulation (EC)No 1901/2006 oftheEuropean Parliament and
oftheCouncil of12December2006onmedicinalproductsforpaediatricuse,asamended byRegulation (EC)
No 1902/2006oftheEuropean Parliament and oftheCouncil of20 December 2006.
24
European Commission's Proposal for a Council Regulation (EEC) concerning the creation ofasupplementaryprotection certificate for medicinal products,COM(90) 101 final.
25
Council Regulation (EEC) No 1768/92 of 18June 1992 concerning the creation of a supplementary
protection certificate for medicinal products.ThetextofRegulation No 1768/92underwent extensive amendment andtheseamendmentswerebrought together inasingle,codified text,inRegulation (EC) No 469/2009
oftheEuropeanParliamentandoftheCouncilof6May2009concerningthesupplementaryprotection certificate
for medicinal products.
26
Regulation (EC)No 1610/96oftheEuropean ParliamentandoftheCouncilof23July 1996 concerning
thecreation ofasupplementary protection certificate for plant protection products.
27
In particular Recital (4)ofRegulation (EC)No 469/2009.
28
SeeRecital (9)ofRegulation (EC) No 469/2009 and Recital (11) ofRegulation (EC) No 1610/96.
128
C. TbeEU Battleground: Data Exclusivity, Patents, and SPCs
originator firms by acting as a bar to generic competition. To that limited extent, data
exclusivity andpatent rights (including SPCs) maybeconsidered tobeoverlapping, butthe
purpose underlying theexclusivity that isconferred byeachofthem isdifferent. Data exclusivity is intended to stimulate and protect investment in expensive and time-consuming
clinical trials. Patents are intended to stimulate and protect inventive activity, but not
necessarily labour and investment. 29 Theessential rationale behind SPCs is to compensate
for time lost during the twenty year patent term (patent term erosion), whilst clinical trials
are undertaken and regulatory approval is obtained.
Inboth theEUandtheUSA,dataexclusivityisspecifically linkedtotheinvestmentinclinical 6.34
studiesthat hasbeen made.Only investments thathavebeen madeinsubstantial new studies
on thesafety and efficacy of new active substances (andnot trials on products that involve
simple variations to existing drugs, or line extensions) areentitled to the protection. So,in
general, clinical research that isintended onlytodemonstrate thesafetyandefficacy ofvariationstoexistingmedicinesisnotintended toberewardedwith anewextended periodofdata
exclusivity.Wewill analyse indetail howthelimitsondata exclusivity playoutinpracticein
the EU,asthis isan important and evolvingareaof thelaw.
In the EU, it ispossible to draw a clear distinction between the patent system on the one 6.35
hand and thedrug approval system (including thedata exclusivity framework) on the other
hand. Indeed, theEuropean Commission hasactivelydiscouraged theregulatory authorities
in the member states from making their consideration of the compliance of generic medicineswith regulatory approval standards conditional upon clearance ofthe patent protected
status of active ingredients. 30
By contrast, in the USA, the patent regime and the generic drug approval process are 6.36
intertwined, in certain respects at least, by virtue of the Hatch-Waxman Act. A detailed
description of the complex legal machinery of Hatch-Waxman isoutside the scope of this
article,butinbrief, itpermits generic manufacturers tofileanabbreviated newdrug application (ANDA) before thepatents of the originator companies have expired. Ageneric manufacturer must certify either that their product does notinfringe anyrelevant patents listed in
the Orange Book—a list ofapproved drug products that ismaintained bytheUSFood and
DrugAdministration (FDA)—or thatthepatentsinquestion areinvalidor unenforceable. 31
This certification usually triggers a lawsuit for patent infringement bythe originator company.A 180-day period of marketing exclusivity maybe granted to the first generic manufacturer to file an ANDA with an appropriate certification, provided that it wins the
subsequent patent dispute, for example bysuccessfully invalidating a relevant patent or by
proving non-infringement. The 180-day period of exclusivity isan extremely valuable right
29
Patents areof course available in Europe for novel and inventive therapeutic uses of compounds and
sometimes such uses may be discovered during clinical trials. This leaves open the possibility in the EU for
doublerewards (ie,patentsanddataexclusivity),basedonthesameclinicalresearch.However,giventhepaucity
ofcaselawintheEUontheenforcement ofsuch patentsandtheirperceivedweaknessaseffective monopolyrights,
wesuggest thatthisparticular issuewith respecttooverlapisatthemarginsofthepresent debate.
30
See the European Commission's Pharmaceutical Sector Inquiry—Final Report, ibid., page 480:"The
Commission will.. .actagainst patent linkage,asaccordingtoCommunity legislation, marketing authorization bodiescannot take thepatent statusoftheoriginator medicine into account when decidingon marketing
authorizations ofgenericmedicines'.
31
TheHatch-Waxman Actamended theFederal Food, Drug, and CosmeticAct, insertings505(j) which
established theANDAapproval process.AnANDAapplicant mustincludeintheANDA apatent certification,
asdescribed ins 505(j)(5)(b)(iv).
129
Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
to secureand ithas madetheUS market anattractive onefor thoseseekingtomarket generic
drug products. No such right exists in the EU.
6.37 The balance of incentives conferred by patents and data exclusivity continues to be the
subject of debate in the USA and has been the subject of discussion in the literature, but in
the EU, less so. One of the reasons for this may be the lack of a legislative framework (like
Hatch-Waxman) that links thepatent and regulatory systemswith areward for generics of a
fixed period of exclusivity (although this may be a topic of future debate, bearing in mind
current pricing and reimbursement pressures on generic medicines in a number of E U
member states).
6.38 A financial opportunity for the generic firms presendy only exists in national EU markets
between the first launch of a generic product, which may bear a price close to that of the
originator product, and thesubsequent genericization ofthemarket for that product, caused
by the entry ofanumber ofother genericcompetitors and leadingeventually to commodity
pricing.In ordertosecurethisfirstmoveradvantage,genericfirmsoften adoptthedual tactic
of an early regulatory filing, coupled with patent litigation. There ishowever at present no
statutory, fixed reward in the EU for being the first generic to market. Some examples
from the case law illustrate the use of the dual strategy that isoften necessary to carve out a
first-to-market generic product opportunity in the EU and demonstrate the fact that data
exclusivity and patents have to be addressed asseparate isssuesby thegeneric firms.
(5) Clopidogrel
6.39 Theblockbuster anticoagulant medicinesPlavix®(Sanofi-aventis) andIscover® (Bristol-Myers
Squibb) contain the activepharmaceutical ingredient (API) Clopidogrel hydrogen sulphate.
These products were granted marketing authorizations in theEU under thecentralized procedure on 15July 1998. Data exclusivitywas expected to continue untilJuly 2008.
6.40 As far as the patent position was concerned, the patent that originally disclosed the Clopidogrel molecule had expired, but in theEU, Sanofi-aventis had obtained afurther patent on
the specific hydrogen sulphate salt form of Clopidogrel32 with SPCs expiring in 2013. This
patent could beavoided bygenericcompetitors by employing adifferent saltof Clopidogrel,
but it was generally assumed that no application for a generic form of Clopidogrel could be
considered by any competent regulatory authority until after the relevant data exclusivity
period had expired.
6.41 O n 21 May 2008, the German regulatory authority (BfArM) then granted marketing
authorizations to a company calledYesPharmaceutical Development Services G m b H 3 3 for
an alternative salt ofClopidogrel (the besylate) on the basisofamixed bibliographical application (under Article lObis of the Directive). In bibliographic applications, preclinical
and clinical trial data can be replaced by scientific literature references, provided that the
applicant can demonstrate well-established medicinal use within the EU for at least ten
years.The ten years ofsystematic and documented use of Clopidogrel were calculated byYes
Pharmaceutical from the date of publication of the results of a pivotal clinical trial.
Furthermore, the data required to support the application included the use of information
32
European patent no0281459 Bl.
ThisGerman companywastheagentfor CimexAG,which could notfiletheapplication itselfbecauseit
wasbasedoutsidethe EU.
33
130
C. TheEU Battleground: Data Exclusivity, Patents, andSPCs
referred to in the European Public Assessment Report (EPAR) that was obtained by Yes
Pharmaceutical by means ofaFreedom ofInformation request. 34
The EPAR is a document that contains an official scientific assessment by the European 6.42
MedicinesAgency (theEMA) oftheclinicalandother datasubmitted byan originator when
making an application for marketing authorization for anew active substance. Itscontent is
therefore drawn up byreference to the underlying datatowhich dataexclusivityattaches.As
indicated above,itwould seem that dataexclusivityshould alsoattach tothesummary of the
assessment of the underlying data in the EPAR,even ifthat summary has been published by
the relevant authority (EPARs arein fact nowpublished on theEMA'swebsite).Thiswas the
viewofSanofi-aventis,35 who applied tothe CologneAdministrative Court to have the decisions of BfArM reviewed. O n 25July 2008, thecourt decided—in apreliminary hearing—
that the objections to the Yes Pharmaceutical authorizations made by Sanofi-aventis were
unfounded. It further decided that the EPARwas not part ofSanofi-aventis' protected data.
The court also decided that abibliographic application relyingon 10years' documented use
could be submitted prior to the end of the relevant 10 year data exclusivity period and then
granted with effect on the first dayafter theexpiryofthat 10year period.The rejection of the
arguments of Sanofi-aventis and BMS were upheld on appeal on 26 September 2008.
It should be noted that these decisionswereonly made on apreliminary basis and although 6.43
theyseem to bepotentially far-reaching inanumber of respects, itisprobablyinadvisable to
draw any firm conclusions about the correctness of the actions ofBfArM. Nevertheless, the
German Clopidogrel decisions came asashock to both sidesof the pharmaceutical industry,
many ofwhom had assumed that the term of data exclusivity for new activesubstances was
sacrosanct.
(6) Galanthamine
Case C-527/07 {Generics[UK] Limited) wasreferred to the Court ofJustice in Luxembourg 6.44
in 2009. It concerned a product called Nivalin containing the API galanthamine that was
first authorized to acompany calledWaldheim in 1963inAustria for the treatment ofpolio.
The original dossier for Nivalin was never updated in accordance with the requirements of
Community law upon the accession ofAustria in 1995. Waldheim subsequently withdrew
Nivalin from the market, but galanthamine was then resurrected asadrug for the treatment
ofAlzheimer's disease.Extensive testingwascarried out between 1995 and 1999.This eventually resulted in the submission on 30 March 1999 of a full application for marketing
authorization 36 for galanthamine. The submission was made to the Swedish competent
authority by Janssen-Cilag AB. A Swedish marketing authorization for galanthamine
(subsequently sold under the brand name Reminyl®) was granted on 1March 2000 and its
34
Seethesummary byDr Christian B.Fuldainan onlinepublication bytheJonesDaylawfirm,at <http://
www.jonesday.com/files/Publication/16a3768f-10a5-4f6cl-9525-5efal57bl54f/Presentation/
PublicationAttachment/3ba3blc0-57cl^e57-b838-0629d789527a/Update%20German%20Plavix.pdf>
lastvisited 20 February 2012.
35
In apressreleaseissuedbySanofi-aventis on 29July2008, thecompany said:
Sanofi Aventis considers that these [German] marketing authorizations, which Sanofi-aventis is
convinced relyon data originating from Sanofi-aventis/Bristol-Myers Squibb—the originators of
Plavix®/Iscover®—should never have been accepted for any reviewbyany EU regulatory agencies
until after data protection expired onJuly 15[2008].
36
Pursuant toArticle4 ofDirective65/65,nowArticle 8ofDirective 2001/83/EC.
131
Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
authorization in other member states (including the UK) followed.37 Galanthamine is an
example ofa molecule forwhich 10year periods ofdata exclusivity (in some countries) and
a period of patent protection were achieved in Europe in respect of the new Alzheimer's
indication, 38 despite the fact that the compound was both old and already known to have
anti-cholinesterase properties. The relevant patent expired in January 2007, but SPCs for
galanthamine were granted, including one that was obtained in the UK, 39 which was set to
expire on 15January 2012.
6.45 Generics [UK] Limited ('Generics [UK]') 40 sought to enter the EU market early with a
genericversion of Reminyl®.For the regulatory limb of their earlymarket entry strategy, on
14 December 2005, Generics [UK] submitted an application to the relevant UK authority
(theMHRA) for a marketing authorization for agenericform ofgalanthamine, using as the
basis ofits application Article 10(1) of the Directive and specifying Nivalin as the reference
medicinal product. The M H R A rejected the application, stating that Nivalin could not be
usedasthereference medicinal product forthepurposes ofArticle 10(1),sinceitsdossier had
not been updated so as to bring it into compliance with the requirements of Community
legislation upon the accession ofAustria. Generics [UK] challenged this rejection by means
ofjudicial review of the MHRA's decision.The administrative court decided to staythe proceedingswhilst clarification wassought from the Court ofJusticeonwhether aproduct such
asNivalin could beareference medicinal product for thepurposesofanabridged application
underArticle 10(1).
6.46 In arelativelyshort judgment issued on 18June 2009, the Court ofJustice emphasized that
thepurpose ofthe Community medicines legislation in requiring the results of toxicological
andpharmacological testsand clinical trialstobesubmitted insupport ofamarketing authorization is to ensure that medicines are safe and efficacious. The abridged procedure in
Article 10hasasitsobjective the avoidanceofunnecessary testson humans and animals, but
theessential aim ofthe rules istosafeguard public health. Only when the competent authority has been provided with all relevant particulars and documents relating to the reference
medicinal product and has been satisfied that the generic product in relation to which
approval issought is so similar to the reference product that it does not differ significandy
with respect to safety and efficacy may a marketing authorization be granted under the
abridged procedure. 41
6.47 An interpretation of the requirements of the abridged procedure which in effect amounted
to a relaxation of the standards of safety and efficacy prescribed by the rules was therefore
inconsistent with one of the main objectives of the Directive. The Court concluded that in
order to get the benefit of the abridged procedure, the applicant had to show that the reference medicinal product was authorized on the basis of Community law in force at the time
of the application for the reference medicinal product. Nivalin was not such a product and
37
UKmarketing authorization nosPL08557/0039,PL08557/0040,PL08557/0041,and PL08557/0042.
Janssen-Cilag have an exclusivelicenceto market Reminyl® in the EU, apart from the UK and Ireland. Shire
Pharmaceuticals havetheexclusiverightstotheproduct for theUKand Ireland.
38
European patent no 0236684 B1 claims the use of galanthamine in second medical use form: 'Use
of galanthamine or an analogue or a pharmaceutically acceptable acid addition salt thereof for preparing a
medicament for thetreatment ofAlzheimersdiseaseor related dementias'.
39
SPC/GBOO/033.
40
NowtradingasMylan.
41
Seethedescription oftheabridged procedures underArticle 10ofthe Directive.
132
C. TheEU Battleground: Data Exclusivity, Patents,and SPCs
so it could not be a reference medicinal product within the meaning ofArticle 10(2) of the
Directive. 42
This case highlights an important issue for applicants seeking abridged (generic) authoriza- 6.48
tions in Europe.Upon accession to theEU, somemember states (suchasAustria, inthiscase)
did not require the dossiers of existing medicinal products that were alreadyauthorized and
on the market to be updated, in order to meet the rigorous standards of European pharmaceutical law. It is therefore necessary carefully to examine nationally authorized reference
medicinal products to assess their suitability to be a reference medicinal product in an
abridged application. Only those products that have been assessed and authorized by the
relevant authorities in accordancewith thestandardsspecified in theDirectivewillsatisfy the
requirement. 43
Under the patent limb of their market penetration strategy, Generics [UK] challenged both 6.49
the validity and the term of the UK SPC. 44 The case was referred by the English Court of
Appeal to the Court ofJustice. 45 Because ofthe outcome ofthe regulatory limb of the strategy, the result of the patent limb became somewhat moot. However, the Court of Justice
subsequently held in Generics [UK]'sfavour. I n a decision issued on 28July2011, the Court
ofJustice decided that the previous authorization of galanthamine (as Nivalin, in Austria)
was fatal to the grant of a SPC based on the subsequent Reminyl® authorization. 46 Active
ingredients (such asgalanthamine) that had been marketed in old drug products in the EU
that had not gone through the administrative procedures laid down in Community law (ie
without havingundergone safety and efficacy testingto Community lawstandards) were not
within the scope ofRegulation (EC) No 469/2009 for the grant of SPCs.
The galanthamine case serves to emphasize the need for generic firms to address separately 6.50
both thedataexclusivityand patent regimeswithin theEU, whilst maintaining an overarching strategy that encompasses both. It also illustrates the necessity for both limbs of the
strategyto succeed, in order for thegeneric firm toachieveasignificant first mover advantage
over its competitors.
(7) Escitalopram
A final example ofa case in which companies sought to deploy the dual strategy of an early 6.51
regulatoryfilingandpatent nullityproceedingsconcerns theAPIescitalopram. Escitalopram
isanother name for the S-enantiomer ofCitalopram. Citalopram isaracemate,which means
that it exists as a mixture of two enantiomers present in equal proportions, being the
R-enantiomerofCitalopramandtheS-enantiomerofCitalopram (escitalopram). Enantiomers
differ in one structural aspect only: they mirror each other, likealeft hand and a right hand.
Yet this difference can have a profound effect on the respective biological activity of each
enantiomer. In this case,escitalopram proved to bethe biologically active molecule.
42
Paragraph 37ofthe judgment.
Forexample,ithasbeen observed that dossiersand authorizationsinGermany that underwent theprocessof 'Nachzulassung'according to the relevant provision ofthe German Medicines Actshould becapable of
being reference medicinal products in the sense ofDirective 2001/83/EC. Seethe article byB. Friese, (2009)
43
71(8) PHARM IND 1335-1337.
44
45
46
CaseH C 08CO 0231:Generics(UK) Ltd vSynaptechInc,relatingto SPC/GBOO/033.
Generics(UK)Ltdv SynaptechInc[2009] EWCACiv 1119 (16October 2009).
CaseC-427/09: Generics (UK)Ltd vSynaptechInc.
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Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
6.52 The Danish originator company H. Lundbeck A/S ('Lundbeck') was granted a European
patent 47 to escitalopram in 1995. SPCs have been granted in a number of countries that
extend Lundbeck's exclusive rights under this patent until May 2014. In 2001, the relevant
Swedish regulatory authority granted to Lundbeck a marketing authorization for the drug
product Cipralex®— containing escitalopram—following an application for regulatory
approval 11 months earlier.
6.53 Before thedataexclusivityperiod forescitalopram hadexpiredandinadvanceofboth patent
and SPC expiry, a number of companies managed to obtain approvals for generic escitalopram products, with a view to bringing these to market. This resulted in a number of legal
cases in several European countries, on the validity of the Lundbeck patent to escitalopram
andseparatelyon theregulatoryanddataexclusivityissuesarisingoutofthegeneric marketing
authorizations.
6.54 In the Netherlands, the Dutch part of the European patent for escitalopram was revoked by
the first instance court. 48 Lundbeck appealed. 49 Despite the revocation of the patent in first
instance, the generic companies have not yet been able to sell their products on the Dutch
market, because Lundbeck has in the meantime successfully objected to the grant of their
marketing authorizations. The main thrust of Lundbeck's objection was that the generic
companies should not have been allowed to refer to data in the dossier ofLundbeck's 2001
marketing authorization for escitalopram. Becausethe regulatory proceedings have reached
an end in the Netherlands, we will confine ourselves here to a discussion of the main issues
in the Dutch regulatory proceedings.
6.55 Thegenericcompanies argued that in granting themarketingauthorization for escitalopram
in 2001, the Swedish authority had simplyassumed—and not substantively investigated—
the question of whether escitalopram was a new active substance. 50 They contended that
escitalopram should be regarded as a line extension of Citalopram; the data that Lundbeck
had filed in order to obtain its marketing authorization for escitalopram did not relate
to research on a new active substance, because a significant portion ofthat research had
already been carried out in support of an earlier application for authorization of the
racemate, Citalopram, asthe drug product Cipramil®.
6.56 A complicating factor was that part of the data to which Lundbeck claimed exclusivity had
alreadybeen made public invarious literature.Therelevant Dutch authority (the CBG) had
initiallygranted the generic authorizations, byallowingreference to this publicdata, despite
the fact (asthe CBG initially accepted) that the Lundbeck escitalopram dossier was covered
by data exclusivity. Following Lundbeck's objection, the CBG decided that Lundbeck
47
European patent no0347066 Bl.
Decision of the District Court of The Hague of 8 April 2009 in Alfred E. TiefenbacherGmbH v H.
Lundbeck A/S JGR 2009/27. It should be noted that Lundbeck has been successful in a number of other
European countries on therelated patent validityand SPCissues.
49
Decision of the Court of Appeal of The Hague of 24 January 2012, IEPT20120124. By the time of
Lundbeck's appeal, thepatent had expired.Thecaseproceeded on thebasisoftheinvalidityoftheDutch SPC
toescitalopram,basedbothontheinvalidityofthebasicpatentand,bywayofastand-aloneattackonthevalidityoftheSPC,for failure to complywith certain provisionsofRegulation No469/2009.TheCourt ofAppeal
held product claims 1-5 ofthe patent invalid, but upheld claims6and 7.Therefore, the SPCwasconfined to
claims6 and7only.
50
The facts are summarized in an English translation of the CBGs decision of 25 February 2010 that is
availableon itswebsiteat <http://www.cbg-meb.nl/NR/rdonlyres/925652E3-845D-4A28-899E-DF6D0AD
050B9/0/2522010escitalopram.pdf> lastvisited 20February 2012.
48
134
D. Conclusion
was correct and refused to allow the generic companies to refer to the published data, thus
requiring the generic companies to submit appropriate new bridging data of their own.
This decision was appealed.
The Dutch regulatory proceedings then focused on the question ofwhether escitalopram is 6.57
a line extension of Citalopram, ie, whether there was a significant difference in safety and
efficacy between the single enantiomer escitalopram and the racemate, Citalopram. If not,
then the marketing authorizations for Citalopram and escitalopram are part of the same
global marketing authorization. As such, the period of data exclusivity expired when the
protection for the Citalopram data expired, because the date of the earlier, initial Citalopram
(Cipramil®) marketing authorization will 'count' as the starting point for data exclusivity
for every authorization falling within the global authorization. O n the other hand, if the
marketing authorization for escitalopram does not form part of the same global authorization asCitalopram, escitalopram will haveitsown regulatory data exclusivityperiod, starting
on the day itwas granted, in 2001.
On re-examination, theCBG madeitsownsubstantiveassessmentand reached theconclusion 6.58
that escitalopram did not differ significantly from Citalopram in terms of its safety and
efficacy, that escitalopram wasalineextension ofCitalopram and that both marketing authorizations formed part of the same global marketing authorization. However, in a decision
issued by the Administrative Division of the Dutch Council of State on 6July 2011, it was
held that the question ofwhether escitalopram could be regarded as a new active substance
had already been decided by the relevant Swedish authority and this decision could not be
re-opened, 51 regardless of the CBG's own substantive assessment of the position.
Asweconcludethischapter, theescitalopram battleintheEU continues.Forpresentpurposes, 6.59
weagain emphasize that in the EU, thegenericfirmsmusttacklepatents/SPCs and data exclusivityasseparatechallenges to beovercome.Whilst there isclearlysomeoverlap—in terms of
the subject-matter—between the Dutch patent and regulatory cases on escitalopram, these
casesdemonstrate onceagainthatthepatentanddataexclusivityregimesintheEUareseparate
and distinct—procedurally,substantively, and in terms ofthe protection that they confer.
D. Conclusion
Patents, SPCs, and data exclusivityarethekeyelementsin the EU battleground between the 6.60
originator and the generic companies. Whilst patents and data exclusivity are not strictly
overlapping rights, it is usually necessary for a competitor seeking to market a generic drug
product in theEU tocheckboth thepatent/SPC position and theexpiryofthedata exclusivity period, for aparticular drug product ofinterest.The rights conferred by patents and data
exclusivity in the EU are separate and distinct, but not necessarily bullet-proof. There are
significant financial incentives for the generic firms to use patent litigation to avoid or to
revoke patents and to deploy early filing (regulatory) strategies in order to carve out a firstto-market opportunity in the EU. The manufacturers of generic medicines continue to test
the protection conferred bydata exclusivity usingthe abridged procedures prescribed by EU
regulatory law. The Clopidogrel, galanthamine, and escitalopram cases are illustrative of the
use by the generic firms ofsuch dual patent and regulatory strategies.
51
DecisionoftheCouncilofStateof6July2011,LJNBR0506,201000808/1.
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Chapter 6:Patentsand RegulatoryData Exclusivityfor Medicinal Products
E. Summary
6.61 • Patents and SPCs continue to be the main form of legal protection for new active
substances (both small molecules and biologicals) in the field ofmedicines in the EU.
• Extensive preclinical and clinical trials may need to be undertaken to demonstrate a drug
products quality, safety, and efficacy to the relevant regulatory authorities.
• In the EU, data that isprovided in support of the proposed use ofanew active substance
in a medicine may benefit from aperiod ofdata exclusivity.
• Data exclusivity usually lasts for a certain period of time after the initial registration of
a new drug product, during which only the entity that developed the data may use it to
support additional marketing authorizations.
• After the data exclusivityperiod, it ispossible for athird party to seekmarketing approval
for agenericproduct, bysubmitting an abridged application for registration that relies on
the data that hasalready been submitted in support ofthe original product.
• Under Article 10 of Directive 2001/83/EC, an abridged marketing authorization can be
applied for by third parties after eight years and the generic medicinal product may be
marketed after a further two (orthree) extrayears: theso-called 8+2+1 rules.
• Firms seeking to enter the EU market with generic medicinal products must usually wait
until after the relevant data exclusivity period has expired before submitting an abridged
application for marketingapproval.Eventhen,theremaybepatent obstaclestobe overcome
before the path to market is clear.
• Both data exclusivity and patent protection may provide significant barriers to entry for
generic firms seeking to enter the EU market. To the extent that both must usually be
overcome in order to enter the EU market with ageneric drug product, they may be seen
in this limited senseasoverlapping rights.
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