DK2403951T3 - Tumorselektive e1a- og e1b-adenovirusmutanter - Google Patents
Tumorselektive e1a- og e1b-adenovirusmutanter Download PDFInfo
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- DK2403951T3 DK2403951T3 DK10749205.0T DK10749205T DK2403951T3 DK 2403951 T3 DK2403951 T3 DK 2403951T3 DK 10749205 T DK10749205 T DK 10749205T DK 2403951 T3 DK2403951 T3 DK 2403951T3
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Claims (19)
1. Farmaceutisk sammensætning omfattende en farmaceutisk acceptabel excipiens og et rekombinant adenovirus, hvor adenovi russet omfatter en modificeret, regulatorisk E1a-sekvens, hvor mindst ét Pea3-bindingssted, eller en funktionel del deraf, er deleteret, hvor den funktionelle del af det mindst ene Pea3-bindingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til Pea3.
2. Farmaceutisk sammensætning ifølge krav 1, hvor mindst ét nukleotid i området fra -305 til -141 bibeholdes.
3. Farmaceutisk sammensætning ifølge krav 1 eller 2, hvor mindst ét af Pea3 II, Pea3 III, Pea3 IV og Pea3 V, eller en funktionel del deraf, er deleteret, eventuelt hvor genstanden udvalgt fra a), b) og c) er deleteret: a) mindst ét af Pea3 II og Pea3 III eller en funktionel del deraf; b) Pea3 II, eller en funktionel del deraf, og Pea3 III eller en funktionel del deraf og c) mindst ét af Pea3 IV og Pea3 V eller en funktionel del deraf.
4. Farmaceutisk sammensætning ifølge ét hvilket som helst af kravene 1-3, hvor Pea3 I, eller en funktionel del deraf, bibeholdes, eventuelt hvor mindst ét E2F-bind ingssted, eller en funktionel del deraf, bibeholdes, hvor den funktionelle del af det mindst ene E2F-bind ingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til E2F.
5. Farmaceutisk sammensætning ifølge krav 1, hvor det rekombinante adenovirus omfatter deletion af nukleotider, der befinder sig opstrøms for et E1a- initieringssted, hvor de le teringssteder er udvalgt fra: (a) nukleotid -393 til -304; (b) nukleotid -305 til -255; (c) nukleotid -270 til -240; (d) nukleot id -299 t i I -293; (e) nukleotid -270 til -265 eller (f) nukleotid -299 til -293 og nukleotid -270 til -265.
6. Farmaceutisk sammensætning ifølge ét hvilket som helst af kravene 1 til 5 til anvendelse i cancerbehandling.
7. Farmaceutisk sammensætning til anvendelse ifølge krav 6, hvor den farmaceutiske sammensætning er beregnet til etablering af kontakt med en målcelle.
8. Fremgangsmåde in vitro til selektiv ekspression af et peptid i en målcelle, hvilken fremgangsmåde omfatter etablering af kontakt mellem målcellen og et rekombinant adenovirus, hvor adenovi russet omfatter en modificeret, regulatorisk E1a-sekvens, hvor mindst ét Pea3-bindingssted, eller en funktionel del deraf, er deleteret, hvor den funktionelle del af det mindst ene Pea3-b ind ingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til Pea3, forudsat at fremgangsmåden ikke er en fremgangsmåde til behandling af menneskeeller dyrekroppen ved kirurgi eller terapi.
9. Genstand ifølge krav 7 eller 8, hvor det rekombinante virus omfatter en deletionsmutant af den regu lator iske E1a-sekvens operativt bundet til en nukleotidsekvens, der koder for et peptid.
10. Genstand ifølge et hvilket som helst af kravene 7 til 9, hvor målcellen er udvalgt fra en neoplastisk celle og en normal celle.
11. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante virus selektivt udtrykker en E1a-isoform, hvor sekvensen, der koder for E1a-isoformen er operativt bundet til den modificerede regu latori ske E1a-sekvens.
12. Genstand ifølge krav 11, hvor det rekombinante adenovirus selektivt udtrykker E1a-12S eller E1a13S.
13. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante adenovirus i alt væsentligt udelukker ekspression af en E1a-isoform, hvor sekvensen, der koder for E1a-isoformen er operativt bundet til den modi f i ce rede, regu latoriske E1a-sekvens.
14. Genstand ifølge krav 13, hvor den udelukkede E1a-isoform er E1a-12S eller E1a-13S.
15. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante adenovirus endvidere omfatter en dna-sekvens indsat i et E1b-19K-i ndsætn ingssted.
16. Genstand ifølge krav 15, hvor indsætningsstedet befinder sig mellem startstedet for E1b-19K og startstedet for E1b 55K.
17. Genstand ifølge krav 15 eller 16, hvor E1b-19K-indsætningsstedet omfatter en deletion af 202 basepar, der følger efter startstedet for E1b-19K.
18. Genstand ifølge et hvilket som helst af kravene 15 til 17, hvor dna-sekvensen er en sekvens, der koder for en tumornekrosefaktor, eller en funktionel del deraf.
19. Genstand ifølge et hvilket som helst af kravene 15 til 17, hvor dna-sekvensen er en sekvens, der koder for kras, eller en funktionel del deraf.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US15682209P | 2009-03-02 | 2009-03-02 | |
PCT/US2010/025926 WO2010101921A2 (en) | 2009-03-02 | 2010-03-02 | Tumor-selective e1a and e1b mutants |
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DK2403951T3 true DK2403951T3 (da) | 2016-01-11 |
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Application Number | Title | Priority Date | Filing Date |
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DK10749205.0T DK2403951T3 (da) | 2009-03-02 | 2010-03-02 | Tumorselektive e1a- og e1b-adenovirusmutanter |
DK15182086.7T DK3029144T3 (da) | 2009-03-02 | 2010-03-02 | Tumorselektive adenovirus e1a- og e1b-mutanter |
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DK15182086.7T DK3029144T3 (da) | 2009-03-02 | 2010-03-02 | Tumorselektive adenovirus e1a- og e1b-mutanter |
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US (5) | US9073980B2 (da) |
EP (4) | EP4123030A1 (da) |
JP (5) | JP6072414B2 (da) |
KR (4) | KR102020018B1 (da) |
CY (1) | CY1122385T1 (da) |
DK (2) | DK2403951T3 (da) |
ES (2) | ES2557812T3 (da) |
HR (2) | HRP20151396T1 (da) |
HU (2) | HUE046565T2 (da) |
LT (1) | LT3029144T (da) |
PL (2) | PL3029144T3 (da) |
PT (2) | PT3029144T (da) |
SI (2) | SI2403951T1 (da) |
SM (1) | SMT201500329B (da) |
WO (1) | WO2010101921A2 (da) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
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EP4123030A1 (en) | 2009-03-02 | 2023-01-25 | The Regents of the University of California | Tumor-selective e1a and e1b mutants |
KR102089121B1 (ko) | 2013-03-14 | 2020-03-13 | 더 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 종양살상형 아데노바이러스 조성물 |
CN108699566B (zh) | 2016-02-23 | 2023-06-30 | 萨克生物研究学院 | 对病毒动力学影响最小的治疗性腺病毒中的外源基因表达 |
CA3013637A1 (en) | 2016-02-23 | 2017-08-31 | Salk Institute For Biological Studies | High throughput assay for measuring adenovirus replication kinetics |
KR20190128618A (ko) * | 2016-09-27 | 2019-11-18 | 에피센트알엑스, 인코포레이티드 | 면역조정 융합 단백질 |
EP3532082A4 (en) | 2016-12-12 | 2020-08-26 | Salk Institute for Biological Studies | SYNTHETIC ADENOVIRUS TUMOR TARGETING AND THEIR USES |
US10232053B2 (en) * | 2016-12-30 | 2019-03-19 | Trieza Therapeutics, Inc. | Immunomodulatory oncolytic adenoviral vectors, and methods of production and use thereof for treatment of cancer |
JP7242534B2 (ja) | 2017-01-30 | 2023-03-20 | エピセントアールエックス,インコーポレイテッド | 腫瘍選択的なtataボックスおよびcaatボックスの変異体 |
CN110741080A (zh) * | 2017-01-30 | 2020-01-31 | 埃皮辛特瑞柯斯公司 | 多转基因重组腺病毒 |
KR20240032169A (ko) * | 2017-04-10 | 2024-03-08 | 에피센트알엑스, 인코포레이티드 | 재조합 바이러스의 제조 방법 |
EA201990822A1 (ru) | 2017-04-12 | 2020-01-09 | Эписентарикс, Инк. | Иммуномодулирующие слитые белки |
MX2019014059A (es) * | 2017-05-24 | 2020-07-28 | Epicentrx Inc | Adenovirus antiangiogenico. |
EP3630987A4 (en) * | 2017-05-26 | 2021-03-24 | EpicentRx, Inc. | RECOMBINANT ADENOVIRUS WITH TRANSGENS |
EP3688037A4 (en) | 2017-09-27 | 2021-09-15 | EpicentRx, Inc. | IMMUNMODULATORY FUSION PROTEINS |
US11510901B2 (en) | 2018-01-08 | 2022-11-29 | Epicentrx, Inc. | Methods and compositions utilizing RRx-001 combination therapy for radioprotection |
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