DK1578446T3 - Anti-cd33-antistoffer og fremgangsmåde til behandling af akut myeloid leukæmi ved anvendelse heraf - Google Patents

Anti-cd33-antistoffer og fremgangsmåde til behandling af akut myeloid leukæmi ved anvendelse heraf Download PDF

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DK1578446T3
DK1578446T3 DK03779105.0T DK03779105T DK1578446T3 DK 1578446 T3 DK1578446 T3 DK 1578446T3 DK 03779105 T DK03779105 T DK 03779105T DK 1578446 T3 DK1578446 T3 DK 1578446T3
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Mary G Hoffee
Daniel Tavares
Robert J Lutz
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Immunogen Inc
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Claims (16)

  1. ANTI-CD33-ANTISTOFFER OG FREMGANGSMÅDE TIL BEHANDLING AF AKUT MYELOID LEUKÆMI VED ANVENDELSE HERAF
    1. CD33-specifikt antistof omfattende: (i) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGK ATLT ADKS STT A YMQLS SLTSEDS AV Y YC ARE VRLR YFDV WGQGTTVTV SS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSOKNYLAWYQQIPGQSPRLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (ii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGK ATLT ADKS STT A YMOLS SLTSEDS AV YYC ARE VRLR YFDV WGQGTTVIVS S; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIMLIQSPGSLAVSPGERVTMSCKSSQSVFFSSSOKNYLAWYQQIPGQSPKWYW ASTRES OVPDRFTGSOSOTDFTT TTSS VOPEDT ,ΑΤΥΥΓΗΟΥΤ .S S R TFGOGTKT .F.TKR; (iii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: OVOLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGKATLT ADKSSTT AYMQLS SLTSEDS AV YYC AREVRLRYFDVWGQGTTVTVSS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYVV ASTRE S GVPDRFTGS GSGTDFTLTIS S VQPEDL AI YYCHQ YLS SRTFGQGTKLEIKR; (iv) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGKATLT ADKSSTT AYMQLSSLTSEDS AVYYCARE VRLR YFDVWGQGTTVTVSS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIMLTQSPGSLAVSPGERVIMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYWASTRES G VPDRFTGSGS GTDFTLTIS S VQPEDLAIYY CHQYLS S RTFGQGTKLEIKR; (v) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGKATLTADKSSTTAYMQLSSLTSEDSAVYYCAREVRLR YFDVWGQGTTVTVSS; Og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIMLTQSPGSLAVSPGERVIMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYW ASTRES G VPDRFTGSGS GTDFTLTIS S VQPEDLAIYYCHQYLS S RTFGQGTKLEIKR; (vi) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGK ATLT ADKS STTAYMQLS SLTSEDS AV YY C ARE VRLRYFDV WGQGTTVTV SS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: ErVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPKLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (vii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGK ATLT ADKS STT A YMQLS SLTSEDS AV YY C ARE VRLRYFDV WGQGTTVTV SS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPKLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (viii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYI HWIKQTPGQGLEWVGVIYPGNDDISYNQKFQGKATLTADKSSTTAYMQLSSLTSEDSAVY YC ARE VRLR YFD VWGQGTT VT VS S; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIMLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYW ASTRES G VPDRFTGSGS GTDFTLTIS S VQPEDLAI YY CHQYLS S RTFGQGTKLEIKR; (ix) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGKATLT ADKS STT AYMQLSSLTSEDS AV YY C ARE VRLRYFDVWGQGTTVTVSS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIMLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYW ASTRES G VPDRFTGSGS GTDFTLTIS S VQPEDLAI YY CHQYLS S RTFGQGTKLEIKR; (x) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGK ATLT ADKS STTAYMQLS SLTSEDS AV YYC ARE VRLRYFDV VVGQGTT VI VS S °g en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIMLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPKLLIYW ASTRES G VPDRFTGSGS GTDFTLTIS S VQPEDLAIYYCHQYLS S RTFGQGTKLEIKR; (xi) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGK ATLT ADKS STT A YMQLSSLTSEDS AV YY C ARE VRLRYFDVWGQGTTVTV SS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIMLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPKLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (xii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGK ATLT ADKS STT A YMQLS SLTSEDS AV YY C ARE VRLRYFDV WGQGTTVTV SS; °g en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (xiii) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGKATLTADKSSTTAYMQLSSLTSEDSAVYYCAREVRLRYFDVWGQGTTVTVSS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYW ASTRES GVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKR; (xiv) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGKATLTADKS STT AYMQLSSLTSEDS A V Y Y C ARE VRLRYFDVWGQGTTVTV SS; °g en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQI PGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGT KLEIKR; eller (xv) en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFKGKATLT ADKS STTAYMQLS SLTSEDS AV YY C ARE VRLRYFDVWGQGTTVTV SS; og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: NIVLTQSPGSLAVSPGERVIMSCKSSQSVFFSSSQKNYLAWYQQ1PGQSPKLLIWASTRESG VPDRFTGS GS GTDFTLTIS S VQPEDLAIYYCHQYLS SRTFGQGTKLEIKR.
  2. 2. CD33-specifikt antistof ifølge krav 1, hvilket antistof omfatter en variabel tungkæderegion omfattende en aminosyresekvens repræsenteret ved: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGNDDIS YNQKFQGKATLT ADKS STTAYMQLS SLTSEDS AV YYC ARE VRLRYFDVWGQGTTVTVSS (SEQ ID NO: 9), og en variabel letkæderegion omfattende en aminosyresekvens repræsenteret ved: EIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQ IPGQSPRLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGT KLEIKR (SEQ ID NO: 10).
  3. 3. Immunkonjugat, der omfatter antistoffet ifølge krav 1 eller 2, er bundet til et lægemiddel eller en prodrug.
  4. 4. Immunkonjugat ifølge krav 3, hvor lægemidlet eller prodrug’en er udvalgt fra gruppen bestående af et maytansinoid, et taxoid, CC-1065, en CC-1065-analog, dolastatin, en dolastatinanalog, methotrexat, daunorubicin, doxorubicin, vineristin, vinblastin, melphalan, mitomycin C, chlorambucil, calicheamicin og derivater deraf.
  5. 5. Sammensætning omfattende antistoffet ifølge krav 1 eller 2 og et lægemiddel eller en prodmg.
  6. 6. Farmaceutisk sammensætning omfattende antistoffet ifølge krav 1 eller 2, eller immunkonjugat eller sammensætning ifølge krav 3 til 5 og et farmaceutisk acceptabelt middel.
  7. 7. Fremgangsmåde in vitro til hæmning af væksten af en celle, der udtrykker CD33, hvilken fremgangsmåde omfatter etablering af kontakt mellem cellen og antistoffet ifølge krav 1 eller 2, immunkonjugatet ifølge krav 3 eller 4, sammensætningen ifølge krav 5 eller en farmaceutisk sammensætning ifølge krav 6.
  8. 8. Antistof ifølge krav 1 eller 2, immunkonjugat ifølge krav 3 eller 4, sammensætning ifølge krav 5 eller farmaceutisk sammensætning ifølge krav 6 til anvendelse som et medikament.
  9. 9. Anvendelse af antistoffet ifølge krav 1 eller 2, immunkonjugatet ifølge krav 3 eller 4, sammensætningen ifølge krav 5 eller den farmaceutiske sammensætning ifølge krav 6 i fremstillingen af et medikament til behandling af cancer.
  10. 10. Antistof ifølge krav 1 eller 2, immunkonjugat ifølge krav 3 eller 4, sammensætning ifølge krav 5 eller farmaceutisk sammensætning ifølge krav 6, til anvendelse i behandling af cancer.
  11. 11. Anvendelse eller antistof, immunkonugat, sammensætning eller farmaceutisk sammensætning til anvendelse ifølge krav 9 eller 10, hvor canceren er udvalgt fra gruppen bestående af akut myeloid leukæmi (AML), kronisk myeloid leukæmi (CML) og pro-myelocytisk leukæmi (PML).
  12. 12. Isoleret polynukleotid, der koder for antistoffet ifølge krav 1 eller 2.
  13. 13. Isoleret polynukleotid, der koder for en let og en tung kæde af antistoffet ifølge krav 1 eller 2.
  14. 14. Rekombinant vektor omfattende polynukleotidet ifølge krav 12 eller 13.
  15. 15. Værtscelle transformeret med den rekombinante vektor ifølge krav 14.
  16. 16. Fremgangsmåde til frembringelse af et CD33-specifikt antistof, hvilken fremgangsmåde omfatter (a) dyrkning af en værtscelle ifølge krav 15 på betingelser, således at værtscellen udtrykker antistoffet, og (b) indsamling af det således udtrykte antistof.
DK03779105.0T 2002-11-07 2003-11-05 Anti-cd33-antistoffer og fremgangsmåde til behandling af akut myeloid leukæmi ved anvendelse heraf DK1578446T3 (da)

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