HUE026374T2 - IGF elleni antitest - Google Patents

IGF elleni antitest Download PDF

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Publication number
HUE026374T2
HUE026374T2 HUE09771361A HUE09771361A HUE026374T2 HU E026374 T2 HUE026374 T2 HU E026374T2 HU E09771361 A HUE09771361 A HU E09771361A HU E09771361 A HUE09771361 A HU E09771361A HU E026374 T2 HUE026374 T2 HU E026374T2
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ser
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val
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gly
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HUE09771361A
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Paul Adam
Eric Borges
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Boehringer Ingelheim Int
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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    • A61K31/282—Platinum compounds
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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    • A—HUMAN NECESSITIES
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57496—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving intracellular compounds
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
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    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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    • C07—ORGANIC CHEMISTRY
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    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
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    • C07K2317/55—Fab or Fab'
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    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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Claims (9)

1. IzoÄ tamin amétÿ a) kötodik a human IGF-l -hzz és IGF-2-hez, oly modon, hogy Q m JGFQ éy l€!E~2 IGPG "foeepUrtoz Ι»'έ&δ kotodése gâtlâs ail iærül» és Il I€if~l-raeëfi>l»r*'kdavedl:ette jelityRel gallay ala koriil, h) kétédik az epir» és patkanyeredeti IQlM-hez c) nem köivkiik a human mznlmhoz; aboi m emlfioi antdesNsdlakpIa egy ùlyai äuifei-molekula, amély rendelkozik €DR~ régiôkkal, atîtelyek tartalmazzâk a következo andaosav-sz#:v^acilkat: SEQ ID NO:21 (CDR!), SEQ ID NO:22 (€DR2) és SEQ II) NO:23 (CDR3), ës sœely Äidelkedk könnyü Mnc CD:R~régidkka!, amëlyëk: a kdvœfkëzi ammos^szakveacllkat tarlalmazaak: SEQ ID NO:24 (CDR! ), SEQ ID NO:25 (CDR2) és SEQ ID NO:26 (CDR3);, 2, A2 it Igenypon); azëAôit antftëstABoIekô^ amaly tëgdelkgpk egy vaiiâbllk Bëhëk lâacoak amply ÂtataazzaaSEQ II>N0:2J aisipusav-saekvandai il Az I, igenyptsht szeAntl aidÎtasi-MûkWa, antely rpnädkezlk egv vanahills këanyü iànccal, amely iariulrnazza a SEQ ID N0:.30 aroinosav-szekvendah
4. Az 1*1, tgiùÿjmnipk Mrrnelyike szerkti aallesl^ppfekgla, amply taxdldaz egy mMz Une Konsums région arneiy a kovetkezokbôl allô csoportbo! van Mvalaszda:: TgGÎ, lg:CI2, igô'3, IgG4, IgM, IgA és IgE konstans regiôk. 5. A 4 Igëpypôt szaxinti antidsômplok A, ahoi az omhRbmehéz lëxfôAonakms réglé m. IgGI, amely taxtahnazza a SEQ ID N0:32 amlmrsav-szekvenciât.
6. Az. 03. igénypontok bârradylke sxerimi anütest-motekula, did a könnyt hme· konstans réglé Igk.
1, A û, Igënypont ssedntl aolilestvmolekala, .aboi a kdnnyil line konsiassi réglé: taxîafeazza a SEQ ID NO:34 ammosav*szekvenaIlk % A 2, vagy 3. igényponi szerimi anlitest-molekula, arndyp#. -van a| egy Bolë? îlhéa, aœely laxtalmasïza. a SEQ !B NO;39 aminosav-szekyeneM ëa I) egy komtyi lànca, anady taxiateazza a SEQ 10210:40 amiîmsa^Azekvmtciât. P;, Ass ί~3. Igeiwponiok bfeoelytke %mmîv· anOtestmmlekula, amely egy Fab-, FCab5}*-vagy agylâbeù Fv-iragmens, Ml iNS-malekela, amely sa 1% Igëpypentôk bizmelyike mmê- anfctmmlekda varlibilis aefe kOdelfa. 11. A 10. igénypent szennîi pHS-moîdkuIa, aroely tarialmazza a 2. igényponi azêrisi aniiîest varilbllls nehéz làncât kodolè SEQ ID NO: 2? màJeotidszekveneiâî es a î, igënypenî szerintl ïfeit'kédofô 8!§Q ID NC); 29 silkfelidszekyesaclat.
12. Bxpres.sziôs vektor, araely îarialmaz egy DNS-aidlekaMt, amely tarîahnazza az 1-9. IglaypentPk bamielvike szerinil anblest-meiekûia Âil: lÉaéil is vad&hllls; Mmnyü lâncât kédokS .fi i ;k i eo U d s ze k ve ne iât. Il, A 12. igéswpoai széæiti ëxpresszîés vekiar, amely iatMmaz egy DNS'-mokkulak: ;pa# larialmazza a SEQ ID HO: 27 és/vagy SEQ ÏD HO: 29 nukleotidszekve^ât 14 b I2. vagy 13. igénypfmt .szerf»i expmssxiôs vektaay amely a variâhllk nehéz lÉlept |a/vagy variabills kênnyO lâncoi kôOolé 'DNH-mpIekolâlpz kapesolva tartaîmaz tov|bh|:ë:gÿ DNSzrnoiekulât, amely a koaslaas tmhëz feeet éyvagy kenstaes klteyi llaeöt kbiolja.
15, Gazfeetb amely a 12., 13. vagy 14. igényponi szerinti expressziôs vekiorok koziü egyel vagy tôbbet hordoz. M, A 13. igënypo szerinti gazdase|t amely egy emlSs sejt
17. Eljarâs az 1~9. igènypontok barmelylke szerinü aotiiest eiôéijitàsara, amely magàban tbglalp egy emlOs :pzôsse|t egy vagy tôbb 12-14. Igènypoeî szerinti expmssziés vekloîral m m mîitesi kmyerëâét m hsztMsfe II. 1|ϋ! m 1~9. Igêsyponlok bérmslyike szetlnl? MtliMt elôéliMsâm, amely magibm foglaïp egy vagy »Ä 12-14, igënypooi szermb vektori iartelmazè enébs gazdaseft megszerzéséi es a gazdä$g|i mnyésztësët,
19. A II. Igénylmniszerlnii «1|éîés, amely maglban foglalja iovabba az antiiesi klnyerë-sét es üsziiîésât is. 20:, Az 1-9. igenyponmfe hârmelyike szsrtpli aatltesl-molekBla gybgyészatbsm tbrténO aik&lraazâsra,
21. Az 1-9. lgiay|kblc& batmelyikeszerinti eltesi-bmlekpla räkos betegsèg kezelésére tbrîénÔ alkahnazàsra, mdy rakos betegsèg a köveikezok közül van kivalasxtva: vérkepzô melszed idtate raies: betegségek, beieërtve a leelézlsekar,, ilmieméka.t és mklipéiai, gyomor^llîeedszed: rlkos bôtegségelg beleërtve $ gyeleesorlkot., gyammräkol« itastag-;¥é^i€^ maimkel, epeMiyagfäkot às epyezstekrakep kSxelebferel, a mâpj|iÂet; vesetlk, pmsziataràk és hûgyhôlyagrâk; eegybgyasiai mies betogsëgsk, heieértve a emlorâkot, pieei%zekrékot edhayakrakeî és: mëhbeMrtya-tâkoi; a bbt* iep és rspk rakos ι®$φφ^ά4$φχ, lëtefcvë é malignes mdsabteakak gfimeekkorl mkes betegsegek, miel # Wites-Mmep a: eeerobîasziômà es a lïwîeg^saarkëma; agpâkok., miel a gtioblaszlörM; aaafké?eik»: miel m esAeoszarkôma, làgvsæôveti ifMoläiie- ::SÂa?këem, bëman:gio:sàalkêma> lüriêrik, kiliniseo %Mm kisspfies tü#rak; meietaËôma, es padsmirigyrak. S· A 21 « tgeaypeei szgrieii aBiitesl-meieWas: alïei a gybgyszar piatmai'aiape kerne-Ikfipiaval, kôzefebbril piaiiaa-alapa paeiifaxelbaÂeplabn vegy gemckabiîpy splafe kaltes lempiaval sorafelb-bek vagy m IGFfk VBGF* HiSR2~estg ÂaroraB, Fût, Fil' kittài vagy ie'for iebibiterai kbaui kivaiasalelt yagyâleÉei imeibiealtaikalmaxäsra vaiô. ......... yy 23. A 22. igénypont seeded aniitest-rnolekuia, ahol as: mTor inhihitera. a aapamide. leessirolinius, deibrolimus vagy avaroiieius. 24 öybgyäszali këseltmaey, amëlf ai !~§, ipeypeelek baraielyike sxedttd aetässl-molekuléi Is agy gyépâsmiiag sliegadhaté iorieket taAalreaA 25. A 24. igânypeet sskaîefi |yégyfeiali késziîmény, arnely tartalmaz mëg agy vagy iobb toylbta gyApaazdi ^atoaey^gei, amelyek a këvaliaz#k këziie»eak kivâlasztva: a) DNS-kârositô hatôanyagok, b} gyépfaaiaiiag aktiv vegypieiek* srmdpk rakes softes gitoljak a jdatvkeii îaakdë- etakai vagy a mitoekes ellaaorzopeetekat, e) antibiotikumok. 26. A 25. Igenypent szerleit gyêgyasâatî kesziieëey. aboi az eielltan egy vagy tibia b) vegyükn a kbvetkexô ir\hibitorokbé! â!lè csoportbôl van ksvàsasztva: az EGFR. VEGF, HER2-neu., AuroraB, Plkl,PB kieaz as PiFerléMbitorai 27. A 24-26:. ippypeetek bâneelyike szcrmii gypgydszati készftmëey râkos batègség: kazeiésere iëdëée alkalésazâsra, mely rakes befagsag: a kbvetkezôk kbzü! vae kivâlasztva; a vérképze reedszart IdeiA rakes betepégekv baleértve a IpekPzisokat, Umlbmàkat és msgletea^ kat, gyomor-bélreedszeri sàkos betegségek, feeleénve a nydocsdtâkoi, gysmsm&ok vastag-végbélràkel, kaseyalmirigyrakel, majrikot epekéiyagraket# ëspevezetekrâket, kôiélebkîëi, 4 'veserÜk*. presztalarâk: ês MgyholyagÄ; «êgylgyâszatl râkes betegsegek, beleértve a emlörakot, petsilszekflket, mlhnyakräkot es mëhbelhârtya-rafcoi; a bôr? leg és nyak r#os megbeiegedlsei, beleihe à maligmis meîanérnâkat; gyesmekkim rakes feeteg-slgel* mini a Wllms-Mfeep: a iilmzsbiasziima Is a ïMiig-ss'ai'kÂa; agyrâkek, lÉk a gliofelasztôma;; szaébmâk, mint m osæillszafkteaÿ läipzoveit szarke», rabiemio-szarkoms, bemaagioszajialma; tiÄak. kifinbsem a aem klsae|tes IliiÄ; mezokiima.« es paizsmiiigyÂ. 28- A 27. igénypont szennii gylgyâszati készîtmény, amely plafena-alapa kemoteràpiâvai, klzelefeferib platma^âlapÉ paeSÄelÄteplaiin «agy pmeltafek^Msplatln keöm teapMval, sorafenib-bel, vagy az EGFR. VEGF, HER2~neu, ÂuroraB, Plkl, P!3 kinâz vagy mTor lÉilili kôziil kiyalaszieii vegyületteî komfeî afelnpzâsra va!4 .Ä Jn-vim e|;âras miGPi Is ÎGF*2 I#ÏN-^eepôrfeez Âéîê Mtbdeségeli ptlâsaza emlessejiben, mely elâzâs magâban feglalja az 1-9. igénypoalok bÉanelpke szerrni m&e#-ïPôlekula «mllteti se|tbe iôrtëaÔi B«|ppaîasak miâlÉi m IC1F-1-reeepicai âltal kSzzeiitett jelaivitek zatamlnFaz IGIG és IGFsâ lItai kllzyetieit pFolilSràeié Is apopièzisellenes hatas gâîlâs a!ékeril| 3§. In viim eprâs m 10F-2 1/R-A inzaiiMeeeptorhez ItMÉtl l#ifedeslpk gatllsém emles sejtfeen* mely eprâs magâban fegfap az 1-9, Ipeypentok bérmeiyîke szerimi anütest-mobkula emlitett sejtbe toéilne bep&atâsàk militai az 1R-A mznlin-reeepter àltal köziietett jlMtvitel la az IBP-2 âltal kêzvetltettprobfers.ciô és apoptèalseilepesibabs gatlâs alâ keml,
31, M Vitro eliarés egy zakos beteg IGF-l-hez es lGF-2*feÉs klllié antiiesi-molekïiâüil vegail kezellse featakozysigânak dknôrzlsére, ahol az emllelt aAest-mokkula az 1-9, igéiiypiiPlek feânnelyike szerpi antitest-mokkula. ahol az emliett e|ârâs magàban tbglâlja a klvelkizfe illpéseket: a| az; 0SSZ-1GF-1 sdpéaek mlrëse m eütleit paekfesbfel vitt blfeloglai jotafeStan; b) âz ëssz-IGF-l szlpersek métém az emllteti péelensbfel: - az emlltett aab-IGF antikst-mokkala fâèkesfeëk t&tônê baÂét; Mveto ·· s?ei felÂpa mintàfeaa, àfeôl az issz-IGF-1 szibphek m (a.) kpésben mlrt bssz>»iGF-t sziÄlz GszoPyltoit afevekeekse JeM, bogy a pleins milyen isèrtlkbea reagâl az eniliiett ami-IGF antitest-niolekulâval végzeit kezelésre.
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