DK2352759T3 - Antistoffer, der neutraliserer humant cytomegalovirus, og anvendelse deraf - Google Patents

Antistoffer, der neutraliserer humant cytomegalovirus, og anvendelse deraf Download PDF

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DK2352759T3
DK2352759T3 DK09745098.5T DK09745098T DK2352759T3 DK 2352759 T3 DK2352759 T3 DK 2352759T3 DK 09745098 T DK09745098 T DK 09745098T DK 2352759 T3 DK2352759 T3 DK 2352759T3
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Antonio Lanzavecchia
Annalisa Macagno
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Inst Res Biomedicine
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Claims (15)

  1. in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitisAntiviral Res, 2004, vol. 64. 103-111 F02171 • MCLEAN et al.Recognition of human cytomegalovirus by human primary immunoglobulins identifies an innate foundation to an adaptive immune responseJ Immunol, 2005, vol. 174, 4768-4778 Γ02171 • LEFRANC et al.lMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domainsDev Comp Immunol, 2003, vol. 27, 155-77 Γ02171 • LEFRANC et al.Unique database numbering system for immunogenetic analysislmmunology Today, 1997, vol. 18, 509- Γ02171 . LEFRANCThe Immunologist, 1999, vol. 7,132-136 ΙΌ2171 . KNAUF et al.J. Bio. Chem., 1988, vol. 263, 15064-15070 ^02171 . GABIZON et al.Cancer Research, 1982, vol. 42, 4734- Γ02171 • CAFISOBiochem Biophys Acta, 1981, vol. 649, 129- Γ02171 • SZOKAAnn. Rev. Biophys. Eng., 1980, vol. 9, 467- Γ0217Ί . POZNANSKY et al.Drug Delivery Systemsl9800000253-315 F02171 . POZNANSKYPharm Revs, 1984, vol. 36, 277- Γ0217Ί . KOHLER, G.MILSTEIN, CNature, 1975, vol. 256, 495-497 Γ02171 • KOZBAR et al.Immunology Today, 1983, vol. 4, 72- Γ02171 • KUBYImmunology20000000 Γ0217Ί • JONES et al.Biotechnol Prog, 2003, vol. 19, 1163-8 Γ02171 . CHO et al.Cytotechnology, 2001, vol. 37, 23-30 Γ0217Ί • CHO et al.Biotechnol Prog, 2003, vol. 19, 229-32 [0217]
    1. Isoleret antistof, eller antigenbindende fragment deraf, der er specifikt for et hCMV-protein gB, hvor antistoffet eller fragmentet (a) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 336, 337 og 338 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 339, 340 og 341; (b) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 316, 317 og 318 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 319, 320 og 321; (c) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 278, 279 og 280 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 281,282 og 283; (d) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 352, 279 og 280 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 281, 282 og 283; (e) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 296, 297 og 298 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 299, 300 og 301; eller (f) omfatter tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 360, 279 og 280 og letkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 281, 282 og 361.
  2. 2. Antistof eller fragment ifølge krav 1, der omfatter variable tung- og letkæderegionssekvenser ifølge henholdsvis SEQ ID NO: 348 og 349, henholdsvis SEQ ID NO: 328 og 329, henholdsvis SEQ ID NO: 290 og 291, henholdsvis SEQ ID NO: 357 og 291, henholdsvis SEQ ID NO: 308 og 309 eller henholdsvis SEQ ID NO: 367 og 368.
  3. 3. Antistof eller fragment ifølge krav 1 eller 2, hvor antistoffet er et humant antistof, et monoklonalt antistof, et enkeltkædeantistof, Fab, Fab’, F(ab’)2, Fv eller scFv.
  4. 4. Isoleret nukleinsyremolekyle, der omfatter en nukleotidsekvens, der koder for antistoffet eller fragmentet ifølge et hvilket som helst af kravene 1 til 3.
  5. 5. Nukleinsyremolekyle ifølge krav 4, der omfatter nukleotidsekvensen ifølge et hvilket som helst af SEQ ID NO: 342-347, 350, 351, 322-327, 330, 331, 284-289, 292, 293, 353-356, 358, 359, 287, 288, 302-307, 310, 311, 362-364, 287, 365, 366, 369 eller 370, eller en nukleotidsekvens, der koder for den samme aminosyresekvens som aminosyresekvensen kodet for af en hvilken som helst af SEQ ID NO: 342-347, 350, 351, 322-327, 330, 331, 284-289, 292, 293, 353-356, 358, 359, 287, 288, 302-307, 310, 311, 362-364, 287, 365, 366, 369 eller 370.
  6. 6. Ekspressionsvektor, der omfatter en nukleinsyre ifølge krav 4 eller 5.
  7. 7. Celle, der er transformeret med en ekspressionsvektor ifølge krav 6.
  8. 8. Sammensætning, der omfatter antistoffet eller fragmentet ifølge et hvilket som helst af kravene 1 til 3, eller nukleinsyren ifølge krav 4 eller 5, og en farmaceutisk acceptabel fortynder eller bærer.
  9. 9. Sammensætning ifølge krav 8, der endvidere omfatter et andet antistof, eller et antigenbindende fragment deraf, der neutraliserer hCMV-infektion.
  10. 10. Sammensætning ifølge krav 9, hvor det andet antistof eller fragment er specifikt for UL128, en epitop dannet af en kombination af ULI30 og UL131A, en epitop dannet af en kombination af ULI 28, ULI 30 og UL131A, en epitop dannet af en kombination af gH, gL, UL128 og UL130, en anden gB-epitop, gH, gL, gM, gN, gO eller en epitop dannet af en kombination af gM og gN.
  11. 11. Sammensætning ifølge krav 10, hvor det andet antistof er specifikt for en epitop dannet af en kombination af UL13 0 og UL131A.
  12. 12. Sammensætning ifølge krav 11, hvor det andet antistof er udvalgt fra: (i) et antistof, der omfatter tung- og letkædesekvenser ifølge henholdsvis SEQ ID NO: 61 og 62; (ii) et antistof, der omfatter variable tungkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 49, 50 og 51 og variable letkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 52, 53 og 54; (iii) et antistof, der omfatter tung- og letkædesekvenser ifølge henholdsvis SEQ ID NO: 13 og 14; (iv) et antistof, der omfatter variable tungkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 1, 2 og 3 og variable letkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 4, 5 og 6; (v) et antistof, der omfatter tung- og letkædesekvenser ifølge henholdsvis SEQ ID NO: 29 og 30; (vi) et antistof, der omfatter variable tungkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 17, 18 og 19 og variable letkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 20, 21 og 22; (vii) et antistof, der omfatter tung- og letkædesekvenser ifølge henholdsvis SEQ ID NO: 45 og 46; (viii) et antistof, der omfatter variable tungkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 33, 34 og 35 og variable letkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 36, 37 og 38; (ix) et antistof, der omfatter tung- og letkædesekvenser ifølge henholdsvis SEQ ID NO: 125 og 126; og (x) et antistof, der omfatter variable tungkædesekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 113, 114 og 115 og variable letkæderegionssekvenser CDR1, CDR2 og CDR3 ifølge henholdsvis SEQ ID NO: 116, 117 og 118.
  13. 13. Anvendelse af antistoffet eller fragmentet ifølge et hvilket som helst af kravene 1 til 3, eller nukleinsyren ifølge krav 4 eller 5, eller sammensætningen ifølge et hvilket som helst af kravene 8 til 12 i fremstillingen af et medikament til behandling af hCMV-infektion.
  14. 14. Antistof eller fragment ifølge et hvilket som helst af kravene 1 til 3, eller nukleinsyre ifølge krav 4 eller 5, eller sammensætning ifølge et hvilket som helst af kravene 8 til 12 til anvendelse i behandlingen af hCMV-infektion.
  15. 15. Fremgangsmåde til fremstilling af antistoffet eller fragmentet ifølge et hvilket som helst af kravene 1 til 3, hvilken fremgangsmåde omfatter (i) dyrkning af cellen ifølge krav 7 og (ii) isolering af antistoffet eller fragmentet.
DK09745098.5T 2008-07-16 2009-07-15 Antistoffer, der neutraliserer humant cytomegalovirus, og anvendelse deraf DK2352759T3 (da)

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