DE06075479T1 - Vorbeugung und Behandlung von amyloidogener Krankheit - Google Patents

Vorbeugung und Behandlung von amyloidogener Krankheit Download PDF

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DE06075479T1
DE06075479T1 DE06075479T DE06075479T DE06075479T1 DE 06075479 T1 DE06075479 T1 DE 06075479T1 DE 06075479 T DE06075479 T DE 06075479T DE 06075479 T DE06075479 T DE 06075479T DE 06075479 T1 DE06075479 T1 DE 06075479T1
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conjugate according
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Dale B. Burlingame Schenk
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Neuralab Ltd
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Abstract

Konjugat, das einen an ein Trägerprotein gebundenen Wirkstoff umfasst, wobei der Wirkstoff:
(i) Aβ,
(ii) ein Aβ-Fragment, das ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert, oder
(iii) ein Analogon oder Mimetikum von (i) oder (ii) ist, wobei das Analogon oder Mimetikum ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert, und
wobei das Trägerprotein eine Immunreaktion gegenüber Aβ erhöht.

Claims (31)

  1. Konjugat, das einen an ein Trägerprotein gebundenen Wirkstoff umfasst, wobei der Wirkstoff: (i) Aβ, (ii) ein Aβ-Fragment, das ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert, oder (iii) ein Analogon oder Mimetikum von (i) oder (ii) ist, wobei das Analogon oder Mimetikum ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert, und wobei das Trägerprotein eine Immunreaktion gegenüber Aβ erhöht.
  2. Konjugat nach Anspruch 1, wobei das Trägerprotein: ein Serumalbumin, Hämocyanin der Schlüssellochschnecke, ein Immunglobulinmolekül, Thyroglobulin, Ovalbumin oder ein Toxoid von einem pathogenen Bakterium ist.
  3. Konjugat nach Anspruch 2, wobei das Trägerprotein Tetanustoxoid, Diphtherietoxoid, E. coli-Toxoid oder H. pylori-Toxoid ist.
  4. Konjugat nach Anspruch 3, wobei das Diphtherietoxoid attenuiertes Diphtherietoxin CRM 197 ist.
  5. Konjugat nach Anspruch 1, wobei das Trägerprotein Choleratoxin ist.
  6. Konjugat nach einem der Ansprüche 1 bis 5, wobei der Wirkstoff an das Trägerprotein durch chemisches Vernetzen gebunden ist.
  7. Konjugat nach einem der Ansprüche 1 bis 5, wobei der Wirkstoff als ein Fusionsprotein mit dem Trägerprotein exprimiert wird.
  8. Konjugat nach Anspruch 7, wobei der Wirkstoff an dem Amino-Terminus an das Trägerprotein gebunden ist.
  9. Konjugat nach Anspruch 7, wobei der Wirkstoff an dem Carboxyl-Terminus an das Trägerprotein gebunden ist.
  10. Konjugat nach Anspruch 7, wobei der Wirkstoff intern an das Trägerprotein gebunden ist.
  11. Konjugat nach einem der Ansprüche 7 bis 10, wobei vielfache Wiederholungen des Wirkstoffs in dem Fusionsprotein vorhanden sind.
  12. Konjugat nach einem der Ansprüche 1 bis 11, wobei der Wirkstoff ein Aβ-Fragment ist, das ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert.
  13. Konjugat nach Anspruch 12, wobei das Aβ-Fragment von der N-terminalen Hälfte von Aβ herrührt.
  14. Konjugat nach Anspruch 12 oder Anspruch 13, wobei das Aβ-Fragment mindestens drei zusammenhängende Aminosäuren von einem natürlichen Aβ-Peptid umfasst.
  15. Konjugat nach Anspruch 14, wobei das Aβ-Fragment mindestens 5 zusammenhängende Aminosäuren von einem natürlichen Aβ-Peptid umfasst.
  16. Konjugat nach Anspruch 15, wobei das Aβ-Fragment mindestens 6 zusammenhängende Aminosäuren von einem natürlichen Aβ-Peptid umfasst.
  17. Konjugat nach einem der Ansprüche 12 bis 15, wobei das Aβ-Fragment: Aβ1-5 oder Aβ1-6 ist.
  18. Konjugat nach einem der Ansprüche 1 bis 11, wobei der Wirkstoff ein Analogon oder Mimetikum von (i) oder (ii) ist, wobei das Analogon oder Mimetikum ein Epitop enthält, das eine ähnliche schützende oder therapeutische Immunreaktion nach Verabreichung an einen Patienten wie ein Aβ-Peptid induziert.
  19. Konjugat nach Anspruch 18, wobei das Analogon mindestens 90% Sequenzidentität zu dem natürlichen Aβ oder Aβ-Fragment aufweist.
  20. Konjugat gemäß einem der Ansprüche 1 bis 19, wobei der Wirkstoff Teil eines längeren Polypeptids ist, das den Wirkstoff zusammen mit anderen Aminosäuren beinhaltet.
  21. Konjugat nach Anspruch 1, wobei der Wirkstoff eine Komponente eines Partikels ist.
  22. Konjugat nach einem der Ansprüche 1 bis 21 für eine Verwendung in der Therapie.
  23. Pharmazeutische Zusammensetzung, die ein Konjugat gemäß einem der Ansprüche 1 bis 22 und eine oder mehrere pharmazeutisch verträgliche Komponenten umfasst.
  24. Pharmazeutische Zusammensetzung gemäß Anspruch 23, die ein Exzipienz umfasst, das für einen oralen Verabreichungsweg oder andere Verabreichungswege geeignet ist.
  25. Pharmazeutische Zusammensetzung gemäß Anspruch 23 oder Anspruch 24, die ein pharmazeutisch verträgliches Adjuvanz umfasst.
  26. Pharmazeutische Zusammensetzung gemäß Anspruch 25, wobei das Adjuvanz für eine gleichzeitige Verabreichung mit dem Wirkstoff vorgesehen ist.
  27. Pharmazeutische Zusammensetzung gemäß Anspruch 26, wobei der Wirkstoff an das Adjuvanz gekoppelt ist.
  28. Pharmazeutische Zusammensetzung gemäß Anspruch 25, wobei das Adjuvanz für eine Verabreichung vor oder nach dem Wirkstoff vorgesehen ist.
  29. Verwendung eines Konjugats gemäß einem der Ansprüche 1 bis 22 zur Herstellung eines Medikaments zum Induzieren einer Immunreaktion gegenüber Aβ und dadurch zur Verhinderung oder Behandlung einer Erkrankung, die mit Amyloidablagerungen von Aβ in dem Gehirn eines Patienten assoziiert ist.
  30. Verwendung nach Anspruch 29, wobei die Erkrankung Alzheimerkrankheit ist.
  31. Verwendung nach Anspruch 29 oder Anspruch 30, wobei der Patient: (a) asymptomatisch und/oder (b) unter 50 ist und/oder (i) vererbte Risikofaktoren, die eine Prädisposition gegenüber Alzheimerkrankheit anzeigen, aufweist oder (ii) keine bekannten Risikofaktoren für Alzheimerkrankheit aufweist.
DE06075479T 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit Pending DE06075479T1 (de)

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US6774097P 1997-12-02 1997-12-02
US67740P 1997-12-02
US8097098P 1998-04-07 1998-04-07
US80970P 1998-04-07

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DE69842082T Expired - Lifetime DE69842082D1 (de) 1997-12-02 1998-11-30 Verhinderung und Behandlung der amyloidogenen Erkrankung
DE69840969T Expired - Lifetime DE69840969D1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit
DE69839647T Expired - Lifetime DE69839647D1 (de) 1997-12-02 1998-11-30 Vorbeugung und behandlung von amyloidogener krankheit
DE69840922T Expired - Lifetime DE69840922D1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit
DE06075479T Pending DE06075479T1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit
DE06075704T Pending DE06075704T1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit
DE1033996T Pending DE1033996T1 (de) 1997-12-02 1998-11-30 Vorbeugung und behandlung von amyloidogener krankheit

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DE69842082T Expired - Lifetime DE69842082D1 (de) 1997-12-02 1998-11-30 Verhinderung und Behandlung der amyloidogenen Erkrankung
DE69840969T Expired - Lifetime DE69840969D1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit
DE69839647T Expired - Lifetime DE69839647D1 (de) 1997-12-02 1998-11-30 Vorbeugung und behandlung von amyloidogener krankheit
DE69840922T Expired - Lifetime DE69840922D1 (de) 1997-12-02 1998-11-30 Vorbeugung und Behandlung von amyloidogener Krankheit

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US (26) US20040171815A1 (de)
EP (5) EP2305282B1 (de)
JP (4) JP4677094B2 (de)
KR (3) KR101248711B1 (de)
CN (1) CN100374151C (de)
AR (1) AR020050A1 (de)
AT (4) ATE493149T1 (de)
AU (1) AU1706199A (de)
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