DK1520588T3 - Anvendelse af antistoffer mod aminophospholipider til cancerbehandling - Google Patents

Anvendelse af antistoffer mod aminophospholipider til cancerbehandling Download PDF

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DK1520588T3
DK1520588T3 DK04007843.8T DK04007843T DK1520588T3 DK 1520588 T3 DK1520588 T3 DK 1520588T3 DK 04007843 T DK04007843 T DK 04007843T DK 1520588 T3 DK1520588 T3 DK 1520588T3
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aminophospholipid
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Philip E Thorpe
Sophia Ran
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Univ Texas
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Claims (50)

1. Sammensætning omfattende en biologisk effektiv mængde af et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, til behandling af cancer ved at dræbe en vaskulariseret tumors tumorvaskulære endotelceller, inducere koagulering i tumorvaskulatur eller destruktion af tumorvaskulatur.
2. Sammensætning til anvendelse ifølge krav 1, hvor anti-aminophospholipid-antistoffet, eller en antigen-bindende region deraf, binder til et aminophospholipid-proteinkompleks på den luminale overflade af en vaskulariseret tumors blodkar.
3. Sammensætning til anvendelse ifølge krav 1 eller 2, hvor sammensætningen omfatter et IgG-eller IgM-anti-aminophospholipid-antistof eller en antigen-bindende region deraf.
4. Sammensætning til anvendelse ifølge krav 1, 2 eller 3, hvor sammensætningen omfatter et IgG-anti-aminophospholipid-antistof.
5. Sammensætning til anvendelse ifølge krav 1, 2 eller 3, hvor sammensætningen omfatter et scFv-, Fv-, Fab'-, Fab- eller F(ab')2-antigen-bindende fragment af et anti-aminophospholipid-antistof.
6. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et monoklonalt anti-aminophospholipid-antistof, eller en antigenbindende region deraf.
7. Sammensætning til anvendelse ifølge krav 6, hvor det monoklonale anti-aminophospholipid-antistof, eller den antigen-bindende fragment deraf, er fremstillet ved en fremstillingsproces, der omfatter: (a) fremstilling af en anti-aminophospholipid-antistofproducerende celle og (b) opnåelse af et monoklonalt anti-aminophospholipid-antistof fra den antistofproducerende celle.
8. Sammensætning til anvendelse ifølge krav 7, hvor den anti-aminophospholipid-antistofproducerende celle er en human patients celle, hvor patienten har en sygdom, der er forbundet med produktion af anti-aminophospholipid-antistoffer.
9. Sammensætning til anvendelse ifølge krav 7, hvor den anti-aminophospholipid-antistofproducerende celle er opnået ved simulering in vitro af en blandet population af lymfocytter fra humant perifert blod med en immunogent effektiv mængde af en aminophospholipidprøve.
10. Sammensætning til anvendelse ifølge krav 7, hvor den anti-aminophospholipid-antistofproducerende celle er opnået ved immunisering af et ikke-humant dyr med en immunogent effektiv mængde af en aminophospholipidprøve.
11. Sammensætning til anvendelse ifølge krav 10, hvor den anti-aminophospholipid-antistofproducerende celle er opnået ved immunisering af en transgen mus, der omfatter et humant antistofbibliotek med en immunogent effektiv mængde af en aminophospholipidprøve.
12. Sammensætning til anvendelse ifølge krav 7, hvor fremstillingsprocessen omfatter: (a) kondensering af den anti-aminophospholipid-antistofproducerende celle med en immortel celle for at fremstille et hybridom, der producerer et monoklonalt anti-aminophospholipid-antistof; og (b) opnåelse af det monoklonale anti-aminophospholipid-antistof fra hybridomet.
13. Sammensætning til anvendelse ifølge krav 7, hvor fremstillingsprocessen omfatter: (a) immunisering af et ikke-humant dyr med en immunogent effektiv mængde af en aminophospholipidprøve; (b) fremstilling af en kollektion af antistof-producerende hybridomer fra det immuniserede dyr; (c) udvælgelse fra kollektionen af et hybridom, der producerer et anti-aminophospholipid-antistof; og (d) dyrkning af det udvalgte hybridom for at tilvejebringe et monoklonalt anti-aminophospholipid-antistof.
14. Sammensætning til anvendelse ifølge krav 13, hvor det immuniserede dyr er en transgen mus, der omfatter et humant antistofbibliotek, og hvor det monoklonale anti-aminophospholipid-antistof er et humant, monoklonalt antistof.
15. Sammensætning til anvendelse ifølge krav 7, hvor fremstillingsprocessen omfatter: (a) opnåelse af anti-aminophospholipid-antistofkodende nukleinsyrer fra den anti-aminophospholipid-antistofproducerende celle og (b) ekspression af nukleinsyreme for at opnå et rekombinant, monoklonalt anti-aminophospholipid-antistof.
16. Sammensætning til anvendelse ifølge krav 7, hvor fremstillingsprocessen omfatter: (a) immunisering af et ikke-humant dyr med en immunogent effektiv mængde af en aminophospholipidprøve; (b) fremstilling af et kombinatorisk immunoglobulin-phagemidbibliotek, der udtrykker RNA isoleret fra milten fra det immuniserede dyr; (c) udvælgelse fra phagemidbiblioteket af en klon, der udtrykker et anti-aminophospholipid-antistof og (d) ekspression af en anti-aminophospholipid-antistofkodende nukleinsyre fra den valgte klon for at tilvejebringe et rekombinant, monoklonalt anti-aminophospholipid-antistof.
17. Sammensætning til anvendelse ifølge krav 16, hvor det immuniserede dyr er en transgen mus, der omfatter et humant antistofbibliotek, og hvor det rekombinante, monoklonale anti-aminophospholipid-antistof er et rekombinant, humant, monoklonalt antistof.
18. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et humant, humaniseret eller delvist humant, kimært anti-aminophospholipid-antistof, eller en antigen-bindende region deraf.
19. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter en dimer, trimer eller multimer af et anti-aminophospholipid-antistof eller antigen-bindende fragmenter deraf.
20. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, der binder til phosphatidylethanolamin på den luminale overflade af en vaskulariseret tumors blodkar.
21. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, der binder til phosphatidylserin på den luminale overflade af en vaskulariseret tumors blodkar.
22. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter mindst to antistoffer, eller antigen-bindende fragmenter deraf, der hvert binder til et særskilt aminophospholipid.
23. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, der binder til phosphatidylethanolamin, phosphatidalserin eller phosphatidalethanolamin.
24. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, fremstillet ved en fremstillingsproces, der omfatter: (a) simulering in vitro af en blandet population af lymfocytter fra humant perifert blod med en immunogent effektiv mængde af en aminophospholipidprøve; (b) immunisering af et ikke-humant dyr med en immunogent effektiv mængde af en aminophospholipidprøve; (c) immunisering af en transgen mus, der omfatter et humant antistofbibliotek med en immunogent effektiv mængde af en aminophospholipidprøve; (d) opnåelse og ekspression af en anti-aminophospholipid-antistofkodende nukleinsyre eller (e) udvælgelse og ekspression af en anti-aminophospholipid-antistofkodende nukleinsyre fra et kombinatorisk immunoglobulin-phagemidbibliotek, der udtrykker RNA isoleret fra milten fra et ikke-humant dyr, der er immuniseret med en effektiv mængde af en aminophospholipidprøve.
25. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter et anti-aminophospholipid-antistof, eller en antigen-bindende region deraf, der binder til lipid-proteinkomplekser, hvor lipiddelen af komplekset er phosphatidylserin eller phosphatidylethanolamin, og proteindelen af komplekset er et hvilket som helst af (k-glycopmtcin I, prothrombin, kininogener og prekallikrein.
26. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er til anvendelse ved induktion af koagulering i tumorvaskulatur efter administration til dyret.
27. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er til anvendelse ved destruktion af tumorvaskulatur efter administration til dyret.
28. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er formuleret til intravenøs administration.
29. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er formuleret som en liposomal formulering.
30. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er beregnet til human administration.
31. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er til anvendelse ved kombination med en diagnostisk effektiv mængde af et detekterbart mærket antistof, eller antigen-bindende fragment deraf, der binder til et aminophospholipid.
32. Sammensætning til anvendelse ifølge krav 31, hvor det detekterbart mærkede antistof, eller det antigen-bindende fragment deraf, omfatter den røntgendetekterbare forbindelse bismuth (111), guld (111), lanthan (III) eller bly (II).
33. Sammensætning til anvendelse ifølge krav 31, hvor det detekterbart mærkede antistof, eller antigen-bindende fragment deraf, omfatter det detekterbare radioaktive ionkobber67, gallium67, gallium68, indium111, indium113, iod123, iod125, iod131, kviksølv197, kviksølv203, rhenium186, rhenium188, rubidium97, rubidium103, technetium99”1 eller yttrium90.
34. Sammensætning til anvendelse ifølge krav 31, hvor det detekterbart mærkede antistof, eller antigen-bindende fragment deraf, omfatter det detekterbare, magnetiske kemespin-resonansisotop cobalt (II), kobber (II), chrom (III), dysprosium (III), erbium (III), gadolinium (III), holmium (III), jem (II), jem (III), mangan (II), neodymium (III), nikkel (II), samarium (III), terbium (III), vanadium (II) eller ytterbium (III).
35. Sammensætning til anvendelse ifølge et hvilket som helst af de foregående krav, hvor sammensætningen er til anvendelse ved kombination med en biologisk effektiv mængde af et andet anticancermiddel.
36. Sammensætning til anvendelse ifølge krav 35, hvor sammensætningen og det andet anticancermiddel indgår i en enkelt farmaceutisk sammensætning.
37. Sammensætning til anvendelse ifølge krav 35, hvor sammensætningen og det andet anticancermiddel indgår i særskilte farmaceutiske sammensætninger.
38. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 35 til 37, hvor det andet anticancermiddel er et kemoterapeutisk, radioterapeutisk, anti-angiogent eller apoptose-inducerende middel.
39. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 35 til 37, hvor det andet anticancermiddel er et konstrukt af et antistof-terapeutisk middel omfattende et målrettet antistof, eller et antigen-bindende fragment deraf, der binder til en overfladeudtrykt, overfladetilgængelig eller overfladelokaliseret bestanddel af en tumorcelle, tumorstroma eller tumorvaskulatur; hvilket målrettet antistof eller fragment deraf er operativt forbundet med et terapeutisk middel.
40. Sammensætning til anvendelse ifølge krav 39, hvor det målrettede antistof, eller antigenbindende fragment deraf, binder til et celleoverfladeantigen af en tumorcelle eller til en bestanddel af tumorstroma.
41. Sammensætning til anvendelse ifølge krav 39, hvor det målrettede antistof, eller antigenbindende fragment deraf, binder til en overfladeudtrykt, overfladetilgængelig, overfladelokaliseret, cytokin-inducerbar eller koaguleringsinducerbar bestanddel af en vaskulariseret tumors intratumorale blodkar.
42. Sammensætning til anvendelse ifølge krav 41, hvor det målrettede antistof, eller antigenbindende fragment deraf, binder til en overfladeudtrykt bestanddel af intratumoral vaskulatur udvalgt fra gruppen bestående af et aminophospholipid, endoglin, en TGFp-receptor, E-selectin, P-selectin, VCAM-1, ICAM-1, PSMA, en VEGF/VPF-receptor, en FGF-receptor, en TIE, ανβ3 integrin, pleiotropin, endosialin og et MHC klasse-II-protein.
43. Sammensætning til anvendelse ifølge krav 41, hvor det målrettede antistof, eller antigenbindende fragment deraf, binder til en overfladelokaliseret bestanddel af intratumoral vaskulatur udvalgt fra gruppen bestående af VEGF/VPF, FGF, TGFfi, en ligand, der binder til en TIE, en tumor-forbundet fibronectin-isoform, spredningsfaktor/hepatocytvækstfaktor (HGF), blodpladefaktor 4 (PF4), PDGF og TIMP.
44. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 39 til 43, hvor det målrettede antistof, eller antigen-bindende fragment deraf, er operativt forbundet med et cytotoksisk middel.
45. Sammensætning til anvendelse ifølge krav 44, hvor det målrettede antistof, eller antigenbindende fragment deraf, er operativt forbundet med et plante-, svampe- eller bakterieafledt toksin, hvor eventuelt og fortrinsvis toksinet er deglycosyleret ricin-A-kæde.
46. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 39 til 43, hvor det målrettede antistof, eller antigen-bindende fragment deraf, er operativt forbundet med en koaguleringsfaktor eller med et antistof, eller et antigen-bindende fragment deraf, der binder til en koaguleringsfaktor.
47. Sammensætning til anvendelse ifølge krav 46, hvor det målrettede antistof, eller antigenbindende fragment deraf, er operativt forbundet med vævsfaktor, trunkeret vævsfaktor eller et derivat deraf, eller med et antistof, eller antigen-bindende fragment deraf, der binder til vævsfaktor, trunkeret vævsfaktor eller et derivat deraf.
48. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 35 til 37, hvor det andet anticancermiddel er et middel udvalgt fra gruppen bestående aftaxol, vineristin, vinblastin, bleomycin, et combretastatin, et podophyllotoksin, TNF-α, angiostatin, endostatin, vasculostatin, en ανβ-.-antagonist, et cytokin, interleukin-4, H202, thrombin, en forbindelse, der interfererer med tubulinaktivitet, et calciumflux-inducerende middel og en calciumionophor.
49. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 35 til 37, hvor det andet anticancermiddel er et middel udvalgt fra gruppen bestående af en phosphotyrosininhibitor, en ikke-hydrolyserbar phosphotyrosinanalog, en pyrimidinanalog, en folinsyre, et platinkoordineringskompleks, en antiandrogen- og en gonadotropinfrigørende hormonanalog.
50. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 35 til 37, hvor det andet anticancermiddel er et middel udvalgt fra gruppen bestående af thalidomid, taxol, paclitaxel, 5-fluoruracil, camptothecin, cisplatin, carboplatin og leuprolid.
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IL140701A (en) 2008-06-05
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