DE919627T1 - Defektive Adenoviren und entsprechende transkomplementante Zelllinien - Google Patents

Defektive Adenoviren und entsprechende transkomplementante Zelllinien

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DE919627T1
DE919627T1 DE0919627T DE98124039T DE919627T1 DE 919627 T1 DE919627 T1 DE 919627T1 DE 0919627 T DE0919627 T DE 0919627T DE 98124039 T DE98124039 T DE 98124039T DE 919627 T1 DE919627 T1 DE 919627T1
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cell line
complementation
adenovirus
region
genome
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DE19824039B4 (de
DE19824039A1 (de
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Jean-Luc Imler
Majid Mehtali
Andrea Pavirani
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Transgene SA
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Transgene SA
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Application filed by Transgene SA filed Critical Transgene SA
Publication of DE919627T1 publication Critical patent/DE919627T1/de
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Claims (26)

EP 98 12 4039.3 Divisonal of EP 94 91 7063.3 Transgene S.A. u.Z.:C1824EP/IV Patentansprüche
1. Komplementationszelllinie, die ein Komplementationselement enthält, das insbesondere einen Teil der E1-Region des Adenovirus-Genoms, &iacgr;&ogr; ausgenommen des 5'-ITR, umfaßt wobei das Komplementationselement einen
defekten Adenovirusvektor in trans komplementieren kann und in das Genom der Komplementationszelllinie integriert oder in einen Expressionsvektor insertiert ist.
2. Komplementationszelllinie nach Anspruch 1, insbesondere enthaltend:
(i) die ganze oder einen Teil der E1A-Region des Adenovirus-Genoms; und (ii) die ganze oder einen Teil mindestens einer Region des Genoms, ausgewählt aus den Regionen E1B, E2 und E4.
3. Komplementationszelllinie nach Anspruch 1, insbesondere enthaltend:
(i) die ganze oder einen Teil der E1A-Region des Adenovirus-Genoms; und (ii) die ganzen oder einen Teil von mindestens zwei der Regionen E1B, E2 und E4 des Genoms.
4. Komplementationszelllinie nach Anspruch 1, insbesondere enthaltend:
(i) die ganze oder einen Teil der E1A-Region des Adenovirus-Genoms; und (ii) die ganzen oder Teile der Regionen E1B, E2 und E4 des Genoms.
5. Komplementationszelllinie nach einem der Ansprüche 2 bis 4, insbesondere enthaltend die ganze oder einen Teil der E1A-Region und die Gesamtheit der E1 B-Region des Adenovirus-Genoms, die frühe Proteine codiert.
6. Komplementationszelllinie nach einem der Ansprüche 1 bis 5, insbesondere
enthaltend einen Teil des Adenovirus-Genoms, ausgewählt aus Hunde-Adenoviren, Vogei-Adenoviren und Menschen-Adenoviren.
7. Komplementationszelllinie nach Anspruch 6, insbesondere enthaltend einen Teil des Genoms eines Typ 5-Menschen-Adenovirus.
8. Komplementationszelllinie nach Anspruch 7, insbesondere enthaltend den Teil des Genoms eines Typ 5-Menschen-Adenovirus,
(i) der sich vom Nucleotid 100 bis zum Nucleotid 5297 erstreckt;
&iacgr;&ogr; (ii) der sich vom Nucleotid 100 bis zum Nucleotid 4034 erstreckt; oder
(iii) der sich vom Nucleotid 505 bis zum Nucleotid 4034 erstreckt.
9. Komplementationszelllinie nach Anspruch 7 oder 8, insbesondere enthaltend den Teil der E4-Region des Genoms eines Typ 5-Menschen-Adenovirus, der sich vom Nucleotid 32800 bis zum Nucleotid 35826 erstreckt.
10. Komplementationszelllinie nach Anspruch 7, insbesondere enthaltend den Teil des Genoms eines Typ 5-Menschen-Adenovirus, der sich vom Nucleotid 505 bis zum Nucleotid 35826 erstreckt.
11. Komplementationszelllinie nach einem der Ansprüche 1 bis 10, enthaltend einen Teil der E1A-Region des Adenovirus-Genoms, die frei ist von ihrem natürlichen Promotor, wobei der Teil unter die Kontrolle eines geeigneten Promotors gestellt ist.
12. Komplementationszelllinie nach Anspruch 11, in der der Teil der E1A-Region unter die Kontrolle eines Promotors gestellt ist, der durch ein nichtadenovirales Transkriptions-Transaktivierungsproteins induzierbar ist.
13. Komplementationszelllinie nach Anspruch 12, in der der Teil der E1A-Region unter die Kontrolle eines Promotors gestellt ist, der durch ein von einem rekombinaten Adenovirusvektor codiertes Transkriptions-
Transaktivierungsprotein induzierbar ist, der ferner ein ein nicht-adenovirales Transkriptions-Transaktivierungsprotein codierendes Gen umfaßt, das unter die Kontrolle von für seine Expression in einer Wirtszelle notwendige Elemente gestellt ist, wobei das Gen insbesondere das das Transkriptions-Transaktivierungsprotein Gal4 codierende Gen von Saccharomyces cerevisiae ist.
14. KomplementationszelHinie nach Anspruch 12 oder 13, wobei der Teil der E1A-Region unter die Kontrolle eines Promotors gestellt ist, der durch ein
&iacgr;&ogr; Transkriptions-Transaktivierungsproteins Gal4 von Saccharomyces cerevisiae
induzierbar ist.
15. KomplementationszelHinie nach einem der Ansprüche 1 bis 14, die unter anderem ein einen Selektionsmarker codierendes Gen enthält.
16. KomplementationszelHinie nach Anspruch 15, wobei das Selektionsgen für Puromycinacetyl-Transferase codiert.
17. KomplementationszelHinie nach Anspruch 15 oder 16, wobei das Selektionsgen unter die Kontrolle eines Promotors gestellt ist, der durch ein von der E1A-Region eines Wildtyp-Adenovirusgenoms codiertes Transkriptions-Transaktivierungsproteins induzierbar ist, insbesondere unter die Kontrolle des Promotors der E2-Region des Genoms.
18. KomplementationszelHinie nach einem der Ansprüche 1 bis 17, die von einer pharmazeutisch verträglichen Zelllinie abgeleitet ist.
19. KomplementationszelHinie nach Anspruch 18, die von einer aus den Linien Vero, BHK, A549, MRC5, W138 und CHO ausgewählten Zelllinie abgeleitet ist.
20. Komplementationszelllinie nach einem der Ansprüche 1 bis 17, die von einer Netzhautzelle eines menschlichen Embryos abgeleitet ist.
21. Komplementationszelllinie nach einem der Ansprüche 1 bis 20, die ein Komplementationselement enthält, das die E1-Funktion eines defekten Adenovirusvektors in trans ergänzen kann, wobei das Komplementationselement insbesondere frei ist von dem 5'-ITR, dem Verpackungsbereich, dem Promotor der E1A-Region und dem Terminationssignal der Transkription der E1B- und plX-Transkriptionseinheiten.
22. Komplementationszelllinie nach Anspruch 21, dadurch gekennzeichnet, daß &iacgr;&ogr; das Komplementationselement der E1-Funktion unter die Kontrolle eines heterologen Promotors, insbesondere des Promotors des murinen PGK-Gens gestellt ist.
23. Komplementationszelllinie nach Anspruch 21 oder 22, dadurch gekennzeichnet, daß das Komplementationselement der E1-Funktion unter die Kontrolle eines heterologen Transkriptionterminationssignals gestellt ist, insbesondere desjenigen des ß-Globulingens von Kaninchen.
24. Arzneimittel, enthaltend als therapeutischen oder prophylaktischen Wirkstoff eine Komplementationszelllinie nach einem der Ansprüche 1 bis 23 in Verbindung mit einem pharmazeutisch verträglichen Träger.
25. Verwendung einer Komplementationszelllinie nach einem der Ansprüche 1 bis 23 zur Herstellung eines Arzneimittels zum Einbringen von DNA-Molekülen in eine Zelle oder in einen eukaryontischen Organismus.
26. Verfahren zur Herstellung eines Adenoviruspartikels, enthaltend einen replikationsdefekten Adenovirusvektor, der durch Deletion von mindestens der gesamten oder einem Teil der E1A-Region von dem Genom eines Adenovirus abgeleitet ist, wobei:
(i) ein Adenovirusvektor in eine Komplementationszelllinie nach einem der Ansprüche 1 bis 23 eingeführt wird, die den Adenovirusvektor in trans
komplementieren kann, um eine transfizierte Komplementationszelllinie
zu erhalten;
(ii) die transfizierte Komplementationszelllinie unter Bedingungen gezüchtet wird, die geeignet sind, die Produktion des Adenoviruspartikels zu
ermöglichen; und
(iii) das Adenoviruspartikel aus der Zellkultur gewonnen wird.
DE0919627T 1993-05-28 1994-05-27 Defektive Adenoviren und entsprechende transkomplementante Zelllinien Pending DE919627T1 (de)

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FR9306482A FR2705686B1 (fr) 1993-05-28 1993-05-28 Nouveaux adénovirus défectifs et lignées de complémentation correspondantes.

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DE919627T1 true DE919627T1 (de) 2000-04-20

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Application Number Title Priority Date Filing Date
DE0919627T Pending DE919627T1 (de) 1993-05-28 1994-05-27 Defektive Adenoviren und entsprechende transkomplementante Zelllinien
DE69425989T Expired - Lifetime DE69425989T3 (de) 1993-05-28 1994-05-27 Neue Komplementations-Zelllinien für defekte adenovirale Vektoren
DE69431372T Expired - Lifetime DE69431372T2 (de) 1993-05-28 1994-05-27 Defekte Adenoviren
DE69426722T Expired - Lifetime DE69426722T2 (de) 1993-05-28 1994-05-27 Defekte adenoviren

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DE69425989T Expired - Lifetime DE69425989T3 (de) 1993-05-28 1994-05-27 Neue Komplementations-Zelllinien für defekte adenovirale Vektoren
DE69431372T Expired - Lifetime DE69431372T2 (de) 1993-05-28 1994-05-27 Defekte Adenoviren
DE69426722T Expired - Lifetime DE69426722T2 (de) 1993-05-28 1994-05-27 Defekte adenoviren

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US (3) US6040174A (de)
EP (6) EP0652968B1 (de)
JP (2) JP4226071B2 (de)
AT (3) ATE223968T1 (de)
AU (1) AU6850394A (de)
CA (1) CA2141212C (de)
DE (4) DE919627T1 (de)
DK (3) DK0919625T3 (de)
ES (3) ES2182212T3 (de)
FR (1) FR2705686B1 (de)
GR (2) GR3034956T3 (de)
PT (3) PT919625E (de)
SG (1) SG55199A1 (de)
WO (1) WO1994028152A1 (de)

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EP0905253A3 (de) * 1992-12-03 2000-11-02 Genzyme Corporation Von allen E4-ORF ausgenommen ORF6 deletierte Adenovirus-Vector
CA2160136A1 (en) * 1993-04-08 1994-10-27 Bruce Trapnell Adenoviral vectors including dna encoding lung surfactant protein
FR2705686B1 (fr) 1993-05-28 1995-08-18 Transgene Sa Nouveaux adénovirus défectifs et lignées de complémentation correspondantes.
US6133028A (en) * 1993-05-28 2000-10-17 Transgene S.A. Defective adenoviruses and corresponding complementation lines
DE69434689D1 (de) * 1993-06-10 2006-05-18 Genetic Therapy Inc Adenovirale vektoren für die behandlung der hämophilie
US20020136708A1 (en) 1993-06-24 2002-09-26 Graham Frank L. System for production of helper dependent adenovirus vectors based on use of endonucleases
JP4190028B2 (ja) * 1993-07-13 2008-12-03 アベンテイス・フアルマ・ソシエテ・アノニム 欠陥組換えアデノウイルスベクター及び遺伝子治療での使用
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PT919627E (pt) 2000-12-29
ES2182212T3 (es) 2003-03-01
US7005277B2 (en) 2006-02-28
DK0919627T3 (da) 2001-01-22
EP0919626A3 (de) 1999-08-18
EP0919627B1 (de) 2000-09-20
WO1994028152A1 (fr) 1994-12-08
FR2705686B1 (fr) 1995-08-18
DE69431372T2 (de) 2003-07-31
JP2009050267A (ja) 2009-03-12
DE69425989D1 (de) 2000-10-26
DK0652968T3 (da) 2001-06-11
ES2151310T5 (es) 2007-10-16
DE69426722T2 (de) 2001-09-20
ES2151310T3 (es) 2000-12-16
JPH07509616A (ja) 1995-10-26
FR2705686A1 (fr) 1994-12-02
EP0652968B1 (de) 2001-02-21
US7067309B2 (en) 2006-06-27
EP0919624A2 (de) 1999-06-02
PT919625E (pt) 2002-11-29
ES2155090T3 (es) 2001-05-01
PT652968E (pt) 2001-07-31
DE69431372D1 (de) 2002-10-17
EP1149916A3 (de) 2007-08-29
EP0919627A3 (de) 1999-07-28
ATE199262T1 (de) 2001-03-15
EP0919625A3 (de) 1999-08-18
JP4226071B2 (ja) 2009-02-18
JP5410721B2 (ja) 2014-02-05
DK0919627T4 (da) 2007-06-25
ATE223968T1 (de) 2002-09-15
DE69425989T2 (de) 2001-02-22
EP0919625B1 (de) 2002-09-11
EP0919624A3 (de) 1999-08-18
EP0919626A2 (de) 1999-06-02
EP0919627B2 (de) 2007-03-14
US6040174A (en) 2000-03-21
CA2141212A1 (fr) 1994-12-08
EP0919625A2 (de) 1999-06-02
CA2141212C (fr) 2007-04-17
DE69426722D1 (de) 2001-03-29
GR3034956T3 (en) 2001-02-28
DK0919625T3 (da) 2002-12-30
GR3035841T3 (en) 2001-08-31
EP0919627A2 (de) 1999-06-02
EP0652968A1 (de) 1995-05-17
SG55199A1 (en) 1998-12-21
US20010049136A1 (en) 2001-12-06
ATE196502T1 (de) 2000-10-15
AU6850394A (en) 1994-12-20
DE69425989T3 (de) 2007-10-18
EP1149916A2 (de) 2001-10-31

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