欧洲专利局2023mRNA技术的洞察力报告

mRNA

technologies

Insightreport

October2023

MRNATECHNOLOGIESINSIGHTREPORT

Executivesummary

ThisreportistheninthpatentinsightreportpublishedbytheEuropeanPatentOffice(EPO),andthesecondreportrelatedtothemedicalsector.1Itsobjectiveistoprovideanoverviewofimportantpatenttrendsinthefieldof

mRNA-basedvaccines,whichisaparticularlydynamicsub-areaofmRNAtechnologies.

Thereportsummarisestheresultsofpatentanalyses

whichwerecarriedoutjointlybysubject-matter

specialistsandpatentknowledgeexpertsattheEPO.Forthisstudy,publiclyavailablepatentinformationdrawnfromtheEPO’sdatabasesofworldwidepatentdatawasanalysed.Patentinformationconstitutesaveryrich

sourceoftechnicalinformationoninventionsforwhichpatentprotectionwassoughtbasedonthecommercialexpectationsoftheapplicants.Patentinformationoftenincludestechnicalandotherinformationthatisnot

availablefromanyothersource.

ThisreportmaybehelpfulasasourceofinformationonmRNA-basedvaccines.Themethodologyonwhichthisreportisbasedcanbeusedfreely,i.e.everyonecanadaptthechosensearchandanalysisapproachtotheirneeds,forexampletofollowtrendsanddevelopmentsinotherestablishedoremergingtechnicalfields.

WhilethenumberofinventionsinthefieldofmRNA-

basedvaccinesisstillratherlow,ithasincreasedvery

dynamicallyoverthelastdecadeataratewhichis

significantlyabovetheincreasegenerallyobservedacrossallfieldsoftechnologycombined.ThefigureonthenextpageshowsthenumberofwhataretermedInternationalPatentFamiliesrelatingtomRNA-basedvaccinesandthenumberinalltechnicalfieldscombined,bytheyearwhentheunderlyinginventionsweremadepubliclyavailableforthefirsttimeandcouldinfluencetheactivitiesof

competitorsandotherresearchers.

PatentapplicantsinthefieldofmRNA-basedvaccinessetafocusonthefollowingpatentapplicationroutes:Internationalpatentapplicationsthatmayresultin

patentprotectioninmorethan150countriesworldwide,USapplications,EPapplications,AUapplications,CA

applications,CNapplications,andJPapplications.ThehighproportionofInternationalpatentapplicationsin

TheEPOpatentinsightreportonmRNAtechnologiesinanutshell:

—focusonmRNA-basedvaccines

—numberofinventionsinthefieldofmRNA-basedvaccinesmultipliedoverthelastdecade

—highergrowthratethanacrossallfieldsoftechnologyingeneral

—upswinginfilingnumbersstartedinthe1990s

—highproportionofInternationalpatent

applications,suggestinghigheconomic

expectationswithregardtothetechnologiesinquestionandmultinationalcommercialisationstrategy

—MostactiveapplicantsinthefieldofmRNA-basedvaccinesarecompaniesanduniversitiesfromtheUnitedStates,Europe,andChina.

thefieldofmRNA-basedvaccinesmaybeinterpretedasanindicationofthesignificanteconomicexpectationsofthepatentapplicantswithregardtothetechnologiesinquestion,aswellasacorrespondingmultinational

commercialisationstrategy.

ThemostactiveapplicantsinthefieldofmRNA-basedvaccinesarecompaniesanduniversitiesbasedinthe

UnitedStates,EuropeandChina.Thelistofactive

applicantsisheadedbythecompaniesModernaand

CureVac,whichhavesubmittedpatentapplicationsforawiderangeofvaccines,whereasotheractiveapplicantshaveremainedratherfocussedonaspecifictargetforvaccination,suchasaparticularpathogenorcancer.

InviewofthehighmomentuminthefieldofmRNA-basedvaccinesandthehighnumberofexciting

inventionsinthisarea,theEPOintendstoupdatethisreportinthefutureandextendittoencompassotherrelevantmRNAtechnologiesaswell.

1MoreinformationaboutEPOpatentinsightreportsandthelistof

currentlyavailablereportsisavailableat

/insight-reports

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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mRNA-basedvaccines:

NumberofInternationalPatentFamilies

Alltechnicalfields:

NumberofInternationalPatentFamilites

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2029

2020

2021

MRNATECHNOLOGIESINSIGHTREPORT

Figure1

mRNA-basedvaccines:NumberofInternationalPatentFamiliesperearliestpublication

NumberofinventionsbyearliestpublicationyearinthefieldofmRNA-basedvaccines,limitedtoInternationalPatentFamilies.InternationalPatentFamiliesgrouptogetherpatentdocumentsrelatingtothesameorsimilarinventionspublishedbytwoormorepatentauthorities.Itisgenerallyassumedthatpatentapplicantsattributegreatereconomicpotentialtotheunderlyinginventionsofthesepatentfamilies,andthattheytendtoseekmoreextensivecommercialisationfromageographicalpointofview.

300

250

200

150

100

50

0

0

900000

800000

700000

600000

500000

400000

300000

200000

100000

Earliestpublicationyear

Source:authors’calculations

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

Contents

Executivesummary

02

Glossary

06

1.

Introduction07

1.1

Aboutthisreport07

1.2

IntroductiontomRNAtechnologies10

2.

Methodologyandsourcesofpatentinformationused16

2.1

Usingpatentinformation16

2.2

MethodologyforthisEPOpatentinsightreport16

2.3

Patentretrieval17

3.

Analysis20

4.Conclusionsandoutlook35

Annex3

4

Notesonthelimitsofthestudy 3

4

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

Abbreviations

AU

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedby

LNP

Lipid-basednanoparticle

IPAustralia,anAustraliangovermentagency

mRNA

Messengerribonucleicacid

CA

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbythe

PCT

PatentCooperationTreaty

CanadianIntellectualPropertyOffice

RNA

Ribonucleicacid

CN

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedby

tRNA

TransferRNA

theChinaNationalIntellectualPropertyAdministration

US

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbytheUnitedStatesPatentandTrademarkOffice

CPC

CooperativePatentClassification

WIPO

WorldIntellectualPropertyOrganization

DE

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbytheGermanPatentandTradeMarkOffice

WO

Two-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbytheWorldIntellectualPropertyOrganization

DNA

Deoxyribonucleicacid

underthePatentCooperationTreaty

DOCDB

EPOworldwidebibliographicdata

EPTwo-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbythe

EuropeanPatentOffice

EPOEuropeanPatentOffice

EPCEuropeanPatentConvention

GBTwo-lettercodeusedtolabelpatent

applicationsprocessedandpublishedby

theIntellectualPropertyOffice(United

Kingdom)

IPCInternationalPatentClassification

JPTwo-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbythe

JapanPatentOffice

KRTwo-lettercodeusedtolabelpatent

applicationsprocessedandpublishedbythe

KoreanIntellectualPropertyOffice

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

Glossary

Cytoplasm

Contentofeucaryoticcellsinsidethecellmembraneexceptforthecellnucleus

Cytosol

Partofthecytoplasm

Enzyme

Proteinactingasacatalyst

Espacenet

FreeonlinepatentsearchingservicedevelopedbytheEPO.Includesinformationonmorethan140milliondocumentsfrom100patentoffices.Espacenetisavailableat

worldwide.

.

Eucaryoticcell

Cellshavingacellnucleus

Internationalpatent

application

PatentapplicationfiledunderthePatentCooperationTreaty.AnInternationalpatentapplicationmayresultinpatentprotectioninmorethan150countries.

InternationalPatentFamily

Apatentfamilyhavingpatentfamilymemberspublishedbyatleasttwodifferentpatentauthorities

Invention

Apracticaltechnicalsolutiontoaproblem

invitro

Outsidethedefaultbiologicalcontextorenvironment

invivo

Withinthedefaultbiologicalcontextorenvironment

Jurisdiction

Country(territory)forwhichapatentorrelatedintellectualpropertyrightmaybegrantedbythecorrespondingintellectualpropertyoffice.

Liposome

Sphericalvesiclewithliquidcontentenclosedbyatleastonelipidbilayer

Patent

Legaltitlegivingthepatentowner(s)therighttoexcludeothersfromusingtheprotectedinventioninacommercialcontext.Theinventionisdefinedintheclaimsofthepatent.

Thedescriptionanddrawingsprovideadditionalinformationandareusedtointerprettheclaims.Theclaims,descriptionanddrawingsofapatentaretogethercalledthe"patent

specification".

Patentapplication

Inthefieldofpatentinformation,theexpression"patentapplication"isusedforboththepatentapplicationitselfandthepatentapplicationpublishedasadocument.

Patentclassificationsystem

Thesetofpatentclassificationsymbolsassignedtocategorisethetechnicalsubject-matterofapatentorutilitymodel.Therearevariouspatentclassificationsystemsusedtodaybynational,regionalandinternationalpatentoffices.

Patentfamily

Asetofpatentdocumentscoveringthesameorsimilartechnicalcontent,dependingonthepatentfamilydefinition.

Thesizeofapatentfamily(familysize)referstothenumberofpatentdocumentsinthatpatentfamily.

ADOCDBpatentfamilyisasetofpatentdocumentsrelatingtopatentapplicationsclaimingpriorityofthesameearlierapplications.Thetechnicalcontentcoveredbythepatent

applicationsinaDOCDBpatentfamilyisconsideredtobeidentical.

Priorityapplication

Inventionscanbeprotectedbypatentsandutilitymodelsinmorethanonecountry.

Foraperiodof12monthsfromthedateoffilinganapplicationforapatentinamember

stateoftheParisConvention,theapplicantortheirsuccessorcanclaimarightofpriorityfromthatapplicationforanysubsequentlyfiledpatentapplicationthatconcernsthesameinvention.Iftherequirementsarefulfilled,thedateoftheearlierapplicationcountsasthedateoffilingofthelaterapplicationforthepurposesofexaminingnoveltyandinventivestep.

Ribosome

IntracellularstructurecomprisingribosomalRNAandribosomalproteinswhichbindsmRNAandtransferRNAtoperformproteinsynthesis

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

1.Introduction

1.1Aboutthisreport

ThisreportistheninthpatentinsightreportpublishedbytheEPO.2Thereportprovidesanoverviewof

technologiesrelatedtomessengerribonucleicacid

(mRNA)deliveredintohumanorothercellstotriggertheproductionofspecificfunctionalproteins,withafocusonmRNA-basedvaccines.mRNA-basedvaccineshave

awiderangeofapplications,e.g.inthepreventionandtreatmentofviralandbacterialinfections,cancerandmalaria,andcontributetotheachievementofUnitedNationsSustainableDevelopmentGoal3(goodhealthandwell-being).3

Untilrecently,mRNAtechnologieswerediscussedby

expertsonly.Lately,thesetechnologieshavereceived

theattentionofawideraudienceduetotheCOVID-19pandemic.Basedonanimpressiveresearcheffort,

mRNA-basedvaccinesagainstSARS-CoV-2were

developedwithinashorttime,andthesevaccinesmadeakeycontributiontocontainingthepandemic.However,therapiddevelopmentofmRNA-basedvaccineswouldnothavebeenpossiblewithoutextensiveresearchintomRNAoverthepastdecades(seeFigure2foratimelineofmilestonesinthefieldofmRNAtechnologies).

TheimpressivemomentuminthefieldofmRNA

technologiescanbeseennotonlyinthewaveof

scientificandtechnicalpublicationsonthissubject,butalsoinanupswinginthenumberofpatentapplicationsrelatedtothesetechnologies.

Withthisreport,wewouldliketoprovideanoverviewofimportantpatenttrendsinthefieldofmRNA-basedvaccines.Forthispurpose,thereportreliesonpubliclyavailablepatentinformation,whichconstitutesaveryrichsourceoftechnicalinformationoninventions

forwhichpatentprotectionwassoughtbasedon

commercialexpectationsoftheapplicants.Patent

informationoftenincludestechnicalinformationthatisnotavailablefromanyothersource.

Togatherrelevantpatentinformationasthebasisforthisreport,searchstrategiesweredevelopedusing

meaningfulkeywordsandrelevantpatentclassificationsymbols.Thesesearchstrategies,whicharedesigned

tostrikeabalancebetweencompletenessandasmallfractionofunrelateddocumentsintheresultsets,werethenusedtocreateabasicdatasetofrelevantpatentdocumentsfromtheEPO’sdatabasesforworldwide

patentdata.Thisbasicdatasetformedthebasisforthesubsequentpatentanalyses.

ThisreportmaybehelpfulasasourceofinformationonmRNA-basedvaccines.Themethodologyonwhichthisreportisbasedcanbeusedfreely,i.e.everyonecanadaptthechosensearchandanalysisapproachtotheirneeds,forexampletofollowtrendsanddevelopmentsinotherestablishedoremergingtechnicalfields.

2MoreinformationaboutEPOpatentinsightreportsandthelistof

currentlyavailablereportsisavailableat

/insight-reports

.

3See

/sustainabledevelopment/health

|07

<

Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

MRNATECHNOLOGIESINSIGHTREPORT

Figure2

SelectionofmilestonesinthedevelopmentofmRNAtechnologies

YearStructureandproductionofmRNA

FormulationofmRNAfordelivery

mRNA-baseddrugapplicationse.g.mRNAvaccines

mRNAingeneediting

1961DiscoveryofmRNAanditsfunction

ProtamineasanRNAcarrierforinvitrouptakebyeukaryoticcells

1963

InductionofinterferonbymRNA

1969

InvitrotranslationofisolatedmRNAinacell-freesystem

1974DiscoveryofmRNAmethylation

1975DiscoveryofmRNA5’cap

Firstinvivonucleicaciddeliverybypolymericparticles

1978

Developmentofliposome-mRNAformulations

1983Capanalogue

1984

InvitromRNAsynthesis(bySP6RNApolymerase)

1985T7RNApolymerasecommercialised

1989

Developmentofcationiclipidnanoparticle(LNP)-mRNA

formulations

SyntheticmRNAincationic

liposomes(structuresmadeof

positively-chargedlipids)deliveredtohumancells,frogembryos

1990

FreemRNAtranslationpost

intramuscularinjectioninmice

Liposome-wrappedmRNAdeliveredtomice

1992

VasopressinmRNAinjectedtoratbraincorrectsdisease

1993

Developmentofliposome-mRNA

influenzavaccineandtestedinmiceDiscoveryofinductionofcellular

immunitybymRNA

1994Developmentofself-amplifying

mRNA

1995

DiscoveryofinductionofhumoralimmunitybymRNA

FirstvaccinationwithmRNAs

encodingcancerantigens:CEA

mRNAcancervaccinetestedinmice

19973'-UTRregulatesmRNAlocalisation,

stabilityandproteinexpression

1999

InvivoinductionofantitumorT-cellresponsebymRNA

2001Anti-reverseCapanaloguefor

superiortranslationefficiencyandextendedhalf-life

FirstclinicaltrialofmRNA-

engineereddendriticcells

2005

NucleosidemodificationreducestheimmunogenicityofmRNA

2006

Poly(A)tailof120nucleosidesandwithfree3’endincreasesmRNAstability

2008

DevelopmentofzincfingermRNAforgeneediting

2009

ClinicaltrialofmRNAtherapeuticsusingprotamine-mRNA

formulations

FirsthumancancerimmunotherapyusingbyinjectionofmRNA

FirstadoptiveimmunotherapywithCARmRNA

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

e.g.mRNAvaccines

YearStructureandproductionofmRNAFormulationofmRNAfordeliverymRNA-baseddrugapplicationsmRNAingeneediting

2010

Preclinicalstudywithintra-nodally

injected(dendriticcell-targeted)

mRNA

2011

Proteinsubstitutionpreclinical

studies:nucleoside-modifiedmRNAcorrectsdisease

Developmentoftranscriptionactivator-likeeffectornuclease(TALEN)mRNAforgeneediting

2012

Preclinicalstudiesofinfluenzaand

RSV-specificmRNAcombination

vaccine

2013m6AmodificationincreasesmRNAstability

FirstclinicaltrialofmRNAvaccineforinfectiousdisease

DevelopmentofCRISPR-Cas9mRNAforgeneediting

2014

ClinicaltrialofLNP-mRNA

formulationsforcancer

immunotherapies

2015

N1-methylpseudouridineenhancestheexpressionandimmuneevasionofmRNA

Firstin-humantestofpersonalisedmRNAcancervaccines

ClinicaltrialofLNP-mRNA

formulationsasinfluenzavaccinesClinicaltrialofLNP-mRNA

formulationsforprotein

replacementtherapies

2017

FirstclinicaltrialofpersonalisedmRNA-basedcancervaccine

FirstreportofmRNALNP

formulationofZikavirusvaccineinvivo

2018Sequenceoptimisationbyuridine

depletionincreasesmRNAactivity

2019

ClinicaltrialsofmRNAvaccinesforcancerandinfectiousdiseases

2020

Authorisationof2COVID-19mRNA-basedvaccines

ClinicaltrialofLNPformulationsdeliveringgene-editingmRNA

componentsforgeneticdisorders

2021

AdjuvantactivityofLNPsinCOVID-19mRNAvaccineswasidentified

InfluentialinventionsinthefieldofmRNA-basedvaccines:

StructureandproductionofmRNA

withincreasedG/Ccontentwhich

isoptimisedfortranslationinits

codedareasforthevaccination

againstsleepingsickness,

leishmaniosisandtoxoplasmosis

EP2331129

Composition

EP1905844

StabilisedmRNA

tumourvaccines

EP2578685

RNAcontaining

modifiednucleosidesandmethods

ofusethereof

Nucleicacidvaccines

EP3329941

RNA-codedbispecific

antibody

EP2603590

Nucleicacid

comprisingorcodingforahistone

stem-loopandapoly(a)sequence

orapolyadenylationsignalfor

increasingtheexpressionofan

encodedprotein

EP3134131

Nucleicacidvaccines

FormulationofmRNAfordelivery

EP1905844

StabilisedmRNAtumourvaccines

EP2590626

LiposomeswithlipidshavinganadvantageousPKA-valueforRNAdelivery

EP3623361

Lipidsandlipid

compositionsforthedeliveryofactiveagents

EP3134131

Nucleicacidvaccines

mRNA-baseddrugapplicationse.g.mRNAvaccines

EP1905844

StabilisedmRNAtumourvaccines

EP3329941

RNA-codedbispecificantibody

comprisingacomplexed(m)RNAandanakedmRNAforprovidingorenhancinganimmunostimulatoryresponseinamammalanduses

thereof

EP2305699

StabilisedmRNA

EP3134131

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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5’Cap

1

MRNATECHNOLOGIESINSIGHTREPORT

1.2IntroductiontomRNAtechnologies

mRNAisanindispensablemoleculeintheclockworkofhumanandothercells.Inthecell,RNAismadefroma

DNAtemplateduringtheprocessoftranscriptionand

mediatesthetransferofgeneticinformationfromthe

cellnucleustothecytoplasmwheretheinformation

istranslatedintoproteinsbyribosomesandtransfer

RNA(tRNA).Theseproteinsareofcrucialimportanceinhumanandanimalorganisms,contributingtogrowth,

maintenanceandstructureoftissues,tobiochemical

processesinthebodyasenzymes,tocellsignallingandtotheimmunesystem,justtonameafewexamples.

mRNAtechnologiesbuildontailoredmRNAtotrigger

cellstoproducespecificproteinswhichmaybeuseful

foravarietyofmedicalapplications.ThereiswidespreadagreementthatwearejustatthebeginningofaneraofefficientmRNA-baseddrugstoaddressawiderangeofdiseases,rangingfromgeneticdiseasesandvariouskindsofcancertoinfectiousdiseases.

mRNAstructureandsynthesis

Fromabiochemicalpointofview,mRNAisessentiallyaspecificrepresentationofgeneticinformationbasedonfournucleotides(adenine,guanine,cytosineanduracil).

mRNAissynthesisedinthecellnucleusduringtranscriptiontoproducepre-mRNAfollowedbyprocessingtomRNA.

Duringtranscription,thegeneticinformationiscopiedfromDNAbyRNApolymerases,formingtheso-calledpre-mRNA.Thismoleculeisthenprocessedbytheadditionofa5’capanda3’poly(A)tail,andbysplicingoutintronsequences

inthenucleustoformthefive-componentmaturemRNAstructure.EachcomponentwithinthemRNAstructurehasaspecificroleinthetransportation,translationandefficientproductionofproteinsbytheribosomesinthecytoplasm(seeFigure3).

Historicaldevelopment

TheisolationofmRNAanditsroleinproteinsynthesiswasdescribedinreferenceliteraturein1961forthefirsttime,buildingonelaborateworkthatstartedinthe1950s.IttookanotherfifteenyearsbeforeresearcherscouldshowthatmRNAcanbedeliveredintohumancellsbyencapsulationinnon-inflammatorypolymers.Shortlyafter,in1978,itwasdemonstratedthatmRNAmoleculescanbedeliveredto

humanandanimalcellsbyusingliposomes.

ElaborateresearchonoptimisingthemRNAstructureanddeliverysystemsconductedbynumerousscientistsledtofurtherbreakthroughsinthemedicaluseofmRNA,suchasthefirstuseofmRNAinacancervaccine(1995)

Figure3

StructureofatypicalhumanmRNAmolecule

5'UTR

Codingregion

3'UTR

Poly(A)tail

5’cap:Asub-structureinthemRNAmoleculewhichprotects

themoleculefromdecompositionbyspecificenzymes.Itplaysa

fundamentalroleinputtingthemRNAmoleculeinapositiontobereadintheribosomeandtohavethegeneticinformationtranslatedduringproteinsynthesis.The5’capremainsuntranslatedduringtheproteinsynthesis.

5’untranslatedregion(5’UTR):Sub-structureinthemRNAwhich

precedesthecodingregionandremainsuntranslatedinmostcasesduringproteinsynthesisintheribosome.Itplaysanimportant

roleinregulatingtheprocessoftranslatinggeneticinformation

intotheprotein.Italsosupportstheribosomeinrecognisingthe

mRNAmoleculeandhelpstomodifythemRNAafterthetranslationprocessiscompleted.

Codingregion:Sub-structurethatcontainsarepresentationofthegeneticinformationfortheproductionofaprotein.

3'

3’untranslatedregion(3’UTR):Sub-structurewhichfollowsthecodingregionandgenerallyremainsuntranslatedduringproteinsynthesisintheribosome.Ithasseveralregulatoryfunctionsforthecopyingofthegeneticinformationinthecellnucleus,the

transportationofthemRNAmoleculefromthecellnucleustotheribosomeandfortheregulationofthetranslationofgeneticinformationduringproteinsynthesis.

Poly(A)tail:ThispartofthemRNAmoleculeisimportantfortheexportofthemoleculefromthecellnucleus,forthetranslation

processandforthestabilityofthemRNAmolecule.ItalsoprotectsthemRNAmoleculefromdegradationandhasanimportant

effectonthelifespanofthemolecule:thepoly(A)tailisgraduallyshortenedovertimeand,belowacertainthreshold,themoleculemaybedegradedenzymatically.

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Contents

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Executivesummary

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1.Introduction

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2.Methodology

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3.Analysis

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4.Conclusions

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Annex

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MRNATECHNOLOGIESINSIGHTREPORT

andthefirstclinicaltrialofapersonalisedmRNA-

basedcancervaccine(2017).TheCOVID-19pandemic

substantiallyacceleratedresearchanddevelopment

regardingmRNAtechnologiesandledtoabreakthroughformRNA-basedvaccines.Today,researchand

developmentismainlydirectedatthefollowingmedicalapplicationsofmRNA:vaccinesfordiseasepreventionandtherapeuticapplications,andtherapeutics,e.g.byproteinreplacement.

Challenges

DespitetheimpressiveprogressmadeinrecentdecadesregardingtheroleofmRNAinthesynthesisofproteinsinhumanandanimalcellsandtheapplicationofmRNAinmedicine,thereisstillextensiveneedforbetter

understandingofthebiochemicalprocessesinvolved

inthesynthesisofmRNA,itstransportandtranslationintoproteins.Atthesametime,thereiswidespread

agreementthatwearejustatthebeginningofaneraofdevelopmentofefficientmRNA-baseddrugstoaddressavarietyofdiseases,includinggeneticdiseases,cancersandinfectiousdiseases.

ThemedicaluseofmRNAtotreatandpreventdiseasesrequiresproductionoffunctionalmRNAinsufficient

quantitieswhicharetranslatedsuccessfullyintoactiveproteins.Additionally,themRNAformedicaluseshouldbesafewithoutserioussideeffectsandunwanted

immunereactions.

Tothisend,itwillbenecessarytofurtheraddressa

numberofobstaclesandopportunitiesforimprovement,includingthefollowingexamples.

Topic

mRNAdesignand

synthesis

Technicalaspect

Stability

Purification

Obje