DK2488204T3 - Terapeutisk kombination og anvendelse af DLL4-antagonistantistoffer og blodtryksnedsættende midler - Google Patents

Terapeutisk kombination og anvendelse af DLL4-antagonistantistoffer og blodtryksnedsættende midler Download PDF

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DK2488204T3
DK2488204T3 DK10824244.7T DK10824244T DK2488204T3 DK 2488204 T3 DK2488204 T3 DK 2488204T3 DK 10824244 T DK10824244 T DK 10824244T DK 2488204 T3 DK2488204 T3 DK 2488204T3
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antibody
antihypertensive agent
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blood pressure
dll4
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Robert Joseph Stagg
Steven Eugene Benner
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Oncomed Pharm Inc
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Claims (17)

1. DLL4-antagonistantistof og et blodtryksnedsættende middel til anvendelse i en fremgangsmåde til lindring eller forebyggelse af forhøjet blodtryk, som forårsages af DLL4-antagonistantistoffet, i et individ, som behandles for cancer med DLL4-antagonistantistoffet, hvor fremgangsmåden omfatter indgivelse af antistoffet i individet og yderligere indgivelse af det blodtryksnedsættende middel i individet for at styre det forhøjede blodtryk, som forårsages af antistoffet.
2. Blodtryksnedsættende middel til anvendelse i en fremgangsmåde til lindring eller forebyggelse af forhøjet blodtryk, som forårsages af behandling med et DLL4-antagonistantistof, hvor fremgangsmåden omfatter indgivelse af det blodtryksnedsættende middel i et individ, som modtager behandling med antistoffet.
3. Antistof og blodtryksnedsættende middel til anvendelse ifølge krav 1, eller det blodtryksnedsættende middel til anvendelse ifølge krav 2, hvor antistoffet specifikt binder til det aminoterminal område af human DLL4 (SEQ ID NO: 11).
4. Antistof og blodtryksnedsættende middel, eller det blodtryksnedsættende middel til anvendelse ifølge et hvilket som helst af kravene 1 til 3, hvor antistoffet omfatter: (i) en variabel region med tung kæde omfattende CDR-aminosyresekvenser CDR1 (SEQ ID NO: 1); CDR2 (SEQ ID NO: 2, SEQ ID NR: 3 eller SEQ ID NO: 4) og CDR3 (SEQ ID NO: 5) og (ii) en variabel region med let kæde omfattende CDR-aminosyresekvenser CDR1 (SEQ ID NO: 7); CDR2 (SEQ ID NO: 8) og CDR3 (SEQ ID NO: 9).
5. Blodtryksnedsættende middel, eller antistof og blodtryksnedsættende middel til anvendelse ifølge et hvilket som helst af kravene 1 til 4, hvor individet lider af forhøjet blodtryk forud for starten af terapi med antistoffet, har risiko for kardiovaskulær sygdom, eller kan ikke på anden måde behandles med en passende dosis DLL4-antagonist uden at udvikle forhøjet blodtryk.
6. Blodtryksnedsættende middel, eller antistof og blodtryksnedsættende middel til anvendelse ifølge et hvilket som helst af kravene 1 til 4, hvor individet ikke har en fortidig historie med forhøjet blodtryk og/eller kardiovaskulær sygdom.
7. Blodtryksnedsættende middel, eller antistof og blodtryksnedsættende middel til anvendelse ifølge et hvilket som helst af kravene 1 til 6, hvor fremgangsmåden yderligere omfatter indgivelse af et yderligere terapeutisk middel.
8. Farmaceutisk sammensætning, som omfatter en DLL4/antagonist og et eller flere blodtryksnedsættende midler, hvor DLL4-antagonisten er et antistof, som specifikt binder human DLL4, til anvendelse i en fremgangsmåde til lindring af forhøjet blodtryk, som er forårsaget af DLL4-antagonisten i et individ, som behandles for cancer med DLL4-antagonisten, hvor fremgangsmåden omfatter indgivelse af antistoffet i individet og yderligere indgivelse af et eller flere blodtryksnedsættende midler i individet for at styre forhøjet blodtryk, der forårsages af antistoffet, hvor antistoffet omfatter: (i) en variabel region med tung kæde omfattende CDR-aminosyresekvenser CDR1 (SEQ ID NO: 1); CDR2 (SEQ ID NO: 2, SEQ ID NR: 3 eller SEQ ID NO: 4) og CDR3 (SEQ ID NO: 5) og (ii) en variabel region med let kæde omfattende CDR-aminosyresekvenser CDR1 (SEQ ID NO: 7); CDR2 (SEQ ID NO: 8) og CDR3 (SEQ ID NO: 9).
9. Farmaceutisk sammensætning til anvendelse ifølge krav 8, yderligere omfattende en farmaceutisk acceptabelt bærer.
10. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 9, hvor fremgangsmåden omfatter måling af blodtrykket af det individ, som behandles med antistoffet, detektere udvikling af forhøjet blodtryk og indgivelse af det blodtryksnedsættende middel for at styre forhøjet blodtryk, der forårsages af antistoffet.
11. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 10, hvor fremgangsmåden yderligere omfatter indgivelse af antistoffet og det blodtryksnedsættende middel i adskilte formuleringer.
12. Blodtryksnedsættende middel, eller antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 3, og kravene 5 til 7 og 9 til 11 for så vidt de afhænger af kravene 1 til 3, hvor antistoffet konkurrerer om specifik binding til human DLL4 med et antistof, der kodes af den plasmid, der er deponeret hos ATCC, som har de-poneringsnr. PTA-8425.
13. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 11, hvor antistoffet kodes af plasmid med ATCC-deponeringsnr. PTA-8425.
14. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 12, hvor antistoffet er monoklonal, humaniseret, kimærisk, human, Fab, Fv eller scFv eller er et bispecifikt antistif.
15. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 11, hvor antistoffet omfatter en variabel region med tung kæde, som omfatter aminosyrerne af SEQ ID NO: 6 og en variabel region med let kæde omfattende aminosyrerne af SEQ ID NO: 10.
16. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor det blodtryksnedsættende middel er udvalgt fra gruppen bestående af: diuretikum, en adrenerg receptorantagonist, en adrenerg recep-toragonist, en kalciumkanalblokker, en ACE-inhibitor, en angiotensin-ll-receptor-antagonist, en aldosteron-antagonist, en vasodilator, en renin-inhibitor og kombinationer deraf.
17. Blodtryksnedsættende middel, antistof og blodtryksnedsættende middel eller sammensætning til anvendelse ifølge krav 16, hvor diuretikum er udvalgt fra gruppen bestående af: furosemid, bumetanid, ethacrynsyre, torsemid, epitizid, hydrochlorothiazid, hydroflumethiazid, chlo-rothiazid, bendroflumethiazid, polythiazid, trichlormethiazid, cyclopenthiazid, methyclothiazid, cyclothiazid, mebutizid, indapamid, chlortalidon, metolazon, quinethazon, clopamid, mefrusid, clofenamid, meticran, xipamid, clorexolon, fenquizon, amilorid, triamteren, eplerenon, benzamil, kaliumcanrenoat, can-renon, spironolacton, mannitol, glucose, urea, conivaptan, relcovaptan, ne-livaptan, lixivaptan, mozavaptan, satavaptan, tolvaptan, demeclocyclin, mer-salylsyre, merallurid, mercaptomerin, mercurophyllin, merethoxyllin, procain, calomel, koffein, theobromin, paraxanthin, theophyllin, acetazolamid, methazolamid, dorzolamid, sulfonamid, topiramat, amanozin, arbutin, chlorazanil, etozolin, hydracarbazin, isosorbid, metochalcon, muzolimin, per-hexilin og ticrynafen; den adrenerge receptorantagonist er udvalgt fra gruppen bestående af: atenolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, timolol, acebuto-lol, bisoprolol, esmolol, labetalol, carvedilol, bucindolol, nebivolol, alprenolol; amosulalol, arotinolol, befunolol, betaxolol, bevantolot, bopindolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butidrinhydrochlorid, butofilolol, carazolol, carteolol, celiprolol, cetamolol, cloranololdilevalol, epanolol, inde-nolol, levobunolol, mepindolol, metipranolol, moprolol, nadoxolol, nipradilol, penbutolol, practolol, pronethalol, sotalol, sulfinalol, talinolol, tertatolol, til-isolol, toliprolol, xibenolol, phenoxybenzamin, prazosin, doxazosin, terazosin, trimazosin, phentolamin, amosulalol, arotinolol, dapiprazol, fenspirid, indora-min, labetalol, naftopidil, nicergolin, tamsulosin, tolazolin, moxonidin, reserpin og yohimbin; den adrenerge receptoragonist er udvalgt fra gruppen bestående af: clonidin, methyldopa, guanfacin, methoxamin, methylnorepinephrin, oxymetazolin, phenylephrin, guanabenz, guanoxabenz, guanethidin, xylazin og tizanidin; kalciumkanalblokkeren er udvalgt fra gruppen bestående af: amlodipin, felo-dipin, nicardipin, nifedipin, nimodipin, isradipin, nitrendipin, aranidipin, bar-nidipin, benidipin, cilnidipin, efonidipin, elgodipin, lacidipin, lercanidipin, ma-nidipin, nilvadipin, nisoldipin, diltiazem, verapamil, bepridil, clentiazem, fen-dilin, gallopamil, mibefradil, prenylamin, semotiadil, terodilin, cinnarizin, fluna-rizin, lidoflazin, lomerizin, bencyclan, etafenon og perhexilin; ACE-inhibitoren er udvalgt fra gruppen bestående af: captopril, zofenopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, fosinopril, cero- napril, casokinins, lactokinins, teprotid, alacepril, cilazapril, delapril, imidapril, moexipril, rentiapril, spirapril, temocapril, moveltipril og trandolapril; angiotensin-ll-receptor-antagonisten er udvalgt fra gruppen bestående af: candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan og valsartan; aldosteron-antagonisten er udvalgt fra gruppen bestående af: eplerenon, canrenon og spironolacton; vasodilatoren er udvalgt fra gruppen bestående af: bencyclan, cinnarizin, citi-colin, cyclandelat, ciclonicat, diisopropylamindichloroacetat, eburnamonin, fasudil, fenoxedil, flunarizin, ibudilast, ifenprodil, lomerizin, nafronyl, nica-metat, nicergolin, nimodipin, papaverin, tinofedrin, vincamin, vinpocetin, vi-quidil, amotriphen, bendazol, benfurodilhemisuccinat, benziodaron, chloraci-zin, chromonar, clobenfural, clonitrat, cloricromen, dilazep, dipyridamol, droprenilamin, efloxat, erythrityltetranitrat, etafenon, fendilin, floredil, gangle-fen, hexestrol bis(P-diethylaminoethyl)ether, hexobendin, itramintosylat, khel-lin, lidoflazin, mannitolhexanitrat, medibazin, nitroglycerin, pentaerythritol-tetranitrat, pentrinitrol, perhexilin, pimefyllin, prenylamin, propatylnitrat, tra-pidil, tricromyl, trimetazidin, trolnitratphosphat, sildenafil, tadalafil, vardenafil, natriumnitroprussid, isosorbidmononitrat, isosorbiddinitrat, pentaerythritol-tetranitrat, theobromin, visnadin, aluminiumnicotinat, bamethan, bencyclan, betahistin, bradykinin, brovincamin, bufeniod, buflomedil, butalamin, cetiedil, ciclonicat, cinepazid, cinnarizin, cyclandelat, diisopropylamindichloroacetat, eledoisin, fenoxedil, flunarizin, hepronicat, ifenprodil, iloprost, inositolniacinat, isoxsuprin, kallidin, kallikrein, moxisylyt, nafronyl, nicametat, nicergolin, ni-cofuranos, nylidrin, pentifyllin, pentoxifyllin, piribedil, prostaglandin E1, suloc-tidil, tolazolin og xanthinolniacinat; og/eller hvor renin-inhibitoren er udvalgt fra gruppen bestående af: aliskiren og remikiren.
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