DK3177723T3 - Aptamerer til anvendelse mod autoantistof-associerede sygdomme - Google Patents
Aptamerer til anvendelse mod autoantistof-associerede sygdomme Download PDFInfo
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Claims (18)
1. Aptamer omfattende en nukleotidsekvens, der opfylder en grammatik, som er defineret af sættet af produktionsregler P:
med betingelserne a. ) Q er mængden af naturlige tal b. ) F er en delmængde af naturlige tal, defineret som F := {X e Q | (X > 1)} c. ) Under anvendelse af F defineres: (1) VXe F3M\M -» CXLCX (2) VX e F3K: K —> CXLBX (3) KXe F3V:V^ CXL (4) VX e F: CX —> BXLBX (5) Y VX ^F\BX^Y[G I d. ) U er en mængde af ikke-terminaler, defineret som U = {S, Μ, Ν, D, Ε, γ, Η, R, Ζ, L, ΒΧ, CX, Κ, V} For ΒΧ og CX se c) e. ) W er en mængde af terminaler, defineret som W = {A, C, G, T,G*} Gx betegner alle terminaler, som kan udledes ud fra b.) og c.)(5) f. ) S e U er startsymbolet til anvendelse ved behandling af autoimmune sygdomme forbundet med autoantistoffer mod G-protein-koblede receptorer, hvor "A" betegner et adeninnukleotid, "C" betegner et cytosinnukleotid, "G" betegner et guaninnukleotid, og "T" betegner et thyminnukleotid, hvis nu-kleotidsekvensen er en DNA-sekvens, og "T" betegner et uracilnukleotid, hvis nukleotidsekvensen er en RNA-sekvens, hvor aptameren ikke omfatter nukleotidsekvensen GGTTGGTGTGGTTGG (SEQ ID No: 22), GGTTGGTGTGGT (SEQ ID NO: 23) eller CGCCTAGGT-TGGGTAGGGTGGTGGCG (SEQ ID No: 24), hvor aptameren er til anvendelse ved behandling af en patient, hos hvem autoantistoffer mod G-protein-koblede receptorer kan detekteres, hvor nukleotidsekvensen har en længde på højst 593 nukleotider.
2. Aptamer til anvendelse ifølge krav 1, hvor aptameren anvendes til at inhi-bere interaktionen af autoantistoffer, der er specifikke for en G-protein-koblet receptor, med dens målproteiner.
3. Aptamer til anvendelse ifølge et hvilket som helst af kravene 1 eller 2, hvor nukleotidsekvensen er en DNA-sekvens, eller hvor nukleotidsekvensen er en RNA-sekvens.
4. Aptamer til anvendelse ifølge et hvilket som helst af de foregående krav, hvor nukleotidsekvensen, der er omfattet af aptameren, er en hvilken som helst af følgende sekvenser: (5'-GTTGTTTGGGGTGG-3' SEQ ID No: 1), (5'-GTTGTTTGGGGTGGT-3' SEQ ID No: 2) (5'-GGTTGGGGTGGGTGGGGTGGGTGGG-3' SEQ ID No: 3), (5'-TTTGGTGGTGGTGGTTGTGGTGGTGGTG-3' SEQ ID No: 4), (5'-TTTGGTGGTGGTGGTTGTGGTGGTGGTGG-3' SEQ ID No: 5), (5'-TTTGGTGGTGGTGGTTTTGGTGGTGGTGG-3' SEQ ID No: 6), (5'-TTTGGTGGTGGTGGTGGTGGTGGTGGTGG-3' SEQ ID No: 7), (5'-TTTGGTGGTGGTGGTTTGGGTGGTGGTGG-3' SEQ ID No: 8), (5'-TGGTGGTGGTGGT-3' SEQ ID No: 9), (5'-GGTGGTGGTGG-3' SEQ ID No: 10), (5'-GGTGGTTGTGGTGG-3' SEQ ID No: 11), (5'-GGTGGTGGTGGTTGTGGTGGTGGTGG-3' SEQ ID No: 12), (5-GGT GGT GGTGGTT GTGGT GGT GGT GGTT GT GGTGGTGGT GGTT GT GGT GGT GG TGG-3' SEQ ID No: 13), (5'-GGTGGTTGTGGTGGTTGTGGTGGTTGTGGTGG-3' SEQ ID No:14), (5'-TTTGGTGGTGGTGGTTGTGGTGGTGGTGGTTT-3' SEQ ID No: 15), (5'-GGTGGTGGTGTTGTGGTGGTGGTGGTTT-3' SEQ ID No: 16), (5'-TTTGGTGGTGGTGGTGTGGTGGTGGTGG-3' SEQ ID No: 17), (5'-TGGTGGTGGT-3' SEQ ID No: 18), (5'-TTAGGGTTAGGGTTAGGGTTAGGG (SEQ ID NO: 20).
5. Aptamer til anvendelse ifølge et hvilket som helst af de foregående krav, hvor nukleotidsekvensen af aptameren har en længde på mindst 4 nukleoti-der, fortrinsvis mindst 8 nukleotider, mere foretrukket mindst 12 nukleotider, og/eller hvor nukleotidsekvensen af aptameren har en længde på højst 120 nukleotider, fortrinsvis højst 100 nukleotider, mere foretrukket højst 80 nukleotider.
6. Aptamer til anvendelse ifølge et hvilket som helst af de foregående krav, hvor aptameren kan interagere med et autoantistof, fortrinsvis et autoantistof, som er specifikt for en G-protein-koblet receptor, fortrinsvis specifikt for en hvilken som helst af den humane G-protein-koblede receptor adrenerg alfa-1-receptor, adrenerg beta-1-receptor, adrenerg beta-2-receptor, endothelin 1 ETA-receptor, muskarin M-receptor, angiotensin II AT1 receptor, PAR-receptorer, MAS-receptor, 5HT4-receptor og/eller M3-receptor.
7. Aptamer til anvendelse ifølge et hvilket som helst af de foregående krav, hvor aptameren er til anvendelse som selektiv bestanddel under terapeutisk aferese af blod eller bestanddele deraf fra en patient, der lider af en autoimmun sygdom forbundet med forekomst af autoantistoffer mod G-protein-koblede receptorer.
8. Aptamer til anvendelse ifølge et hvilket som helst af de foregående krav, hvor den autoimmune sygdom er en blandt kardiomyopati, dilateret kardio-myopati (DCM), peripartum kardiomyopati (PPCM), idiopatisk kardiomyopati, iskæmisk kardiomyopati (iCM), Chagas' kardiomyopati, kemoterapi-induceret kardiomyopati, Chagas' megacolon, Chagas' megaoesophagus, Chagas' neuropati, benign prostatahyperplasi, sklerodermi, Raynauds syndrom, præ-eklamsi, perifer okklusiv arteriesygdom (PAOD), nyre-allograft-afstødning, myokarditis, glaukom, hypertension, pulmonal hypertension, malign hypertension, metabolisk syndrom, alopecia, alopecia areata, migræne, Parkinsons sygdom, epilepsi, klyngehovedpine, multipel sklerose, depression, regionalt smertesyndrom, ustabil angina pectoris, systemisk lupus erythematosus (SLE), skizofreni, Sjogrens syndrom, parodontitis, atrieflimren, vitiligo, hæmolytisk uræmisk syndrom, stiff person-syndrom og/eller medfødt hjerteblok.
9. Anvendelse af en aptamer ifølge et hvilket som helst af kravene 1 til 6 eller 8 til in wfro-detektering af et antistof, der er specifikt for en G-protein-koblet receptor, fortrinsvis den humane G-protein-koblede receptor adrenerg alfa-1-receptor, adrenerg beta-1-receptor, adrenerg beta-2-receptor, endothelin 1 ETA-receptor, muskarin M-receptor, angiotensin II AT1-receptor, PAR-receptorer, MAS-receptor, 5HT4-receptor og/eller M3-receptor, hvor antistoffet, der skal detekteres, er et autoantistof.
10. Anvendelse af aptameren ifølge krav 9, hvor antistoffet er til stede i eller stammer fra en kropsvæske, fortrinsvis en væske fra en menneskekrop, mere foretrukket humant blod, plasma, serum, urin, fæces, synovialvæske, in-terstitiel væske, lymfe, spyt, spinalvæske og/eller tårevæske.
11. Anvendelse af aptameren ifølge krav 10, hvor kropsvæsken udtages fra en person, der lider af eller mistænkes for at lide af en autoimmun sygdom, fortrinsvis en autoimmun sygdom forbundet med tilstedeværelse i serum hos patienten af autoantistoffer, der er specifikke for en G-protein-koblet receptor, mere foretrukket autoimmune sygdomme forbundet med tilstedeværelse i serum hos patienten af autoantistoffer, der er specifikke for adrenerg alfa-1-receptor, adrenerg beta-1-receptor, adrenerg beta-2-receptor, endothelin 1 ETA-receptor, muskarin M-receptor, angiotensin II AT1-receptor, PAR-receptorer, MAS-receptor, 5HT4-receptor og/eller M3-receptor.
12. Aptamer til anvendelse ifølge et hvilket som helst af kravene 1 til 8, hvor aptameren omfatter følgende nukleotidsekvens (5'-GGTGGTGGTGGTTGTGGTGGTGGTGG-3' SEQ ID No. 12).
13. Anvendelse af aptameren ifølge et hvilket som helst af kravene 9 til 11, hvor aptameren omfatter følgende nukleotidsekvens (5'-GGTGGTGGTGGTTGTGGTGGTGGTGG-3' SEQ ID No. 12).
14. Farmaceutisk sammensætning omfattende mindst en aptamer ifølge et hvilket som helst af kravene 1 til 8 og, eventuelt, mindst en farmaceutisk acceptabel excipiens til anvendelse ved behandling af autoimmune sygdomme forbundet med autoantistoffer mod G-protein-koblede receptorer, hvor aptameren er til anvendelse ved behandling af en patient, hos hvem autoantistoffer mod G-protein-koblede receptorer kan detekteres.
15. Farmaceutisk sammensætning til anvendelse ifølge krav 14, hvor den farmaceutiske sammensætning omfattende aptameren anvendes til at inhibe-re interaktionen af autoantistoffer, der er specifikke for en G-protein-koblet receptor, med dens målproteiner.
16. Aferese-søjle omfattende en aptamer ifølge et hvilket som helst af de foregående krav til anvendelse ved behandling af en autoimmun sygdom, hvor den autoimmune sygdom er kardiomyopati, dilateret kardiomyopati (DCM), peripartum kardiomyopati (PPCM), idiopatisk kardiomyopati, iskæmisk kardiomyopati (iCM), Chagas' kardiomyopati, kemoterapi-induceret kardiomyopati, Chagas' megacolon, Chagas' megaoesophagus, Chagas' neuropati, benign prostatahyperplasi, sklerodermi, Raynauds syndrom, perifer okklusiv arteriesygdom (PAOD), præeklamsi, nyre-allograft-afstødning, myokarditis, glaukom, hypertension, pulmonal hypertension, malign hypertension, metabolisk syndrom, alopecia, alopecia areata, migræne, Parkinsons sygdom, epilepsi, klyngehovedpine, multipel sklerose, depression, regionalt smertesyndrom, ustabil angina pectoris, systemisk lupus erythematosus (SLE), skizofreni, Sjogrens syndrom, parodontitis, atrieflimren, vitiligo, hæmolytisk uræmisk syndrom, stiff person-syndrom og/eller medfødt hjerteblok, hvor aptameren er til anvendelse ved behandling af en patient, hos hvem autoantistoffer mod G-protein-koblede receptorer kan detekteres.
17. Aferese-søjle til anvendelse ifølge krav 16, hvor aptameren anvendes som selektiv bestanddel til specifikt at udskille de autoantistoffer, som aptameren specifikt er rettet imod.
18. Fremgangsmåde til fremstilling af en aptamer-oligonukleotid, omfattende følgende trin: I) bestemmelse af en nukleotidsekvens til anvendelse som en aptamerse-kvens omfattende anvendelse af følgende sæt af produktionsregler P:
med betingelserne a. ) Q er mængden af naturlige tal b. ) F er en delmængde af naturlige tal, defineret som F := {X € Q I (X > 1)} c. ) Under anvendelse af F defineres: (1) vXe F3M: M—> CXLCX (2) vXe F3K \K-> CXLBX (3) VXe FlV\V-> CXL (4) VXe F: CX-> BXLBX (5) .Y VXeF: 1 d. ) U er en mængde af ikke-terminaler, defineret som U = {S, Μ, N, D, E, Y, H, R, Z, L, BX, CX, K, V} For BX og CX se c) e. ) W er en mængde af ikke-terminaler, defineret som W = {A, C, G, T, Gx} Gx betegner alle terminaler, som kan udledes ud fra b.) og c.)(5) f. ) S e U er startsymbolet hvor "A" betegner et adeninnukleotid, "C" betegner et cytosinnukleotid, "G" betegner et guaninnukleotid, og "T" betegner et thyminnukleotid, hvis nu-kleotidsekvensen er en DNA-sekvens, og "T" betegner et uracilnukleotid, hvis nukleotidsekvensen er en RNA-sekvens, hvor nukleotidsekvensen til anvendelse som en aptamersekvens ikke omfatter nukleotidsekvensen GGTTGGTGTGGTTGG (SEQ ID No: 22), GGT-TGGTGTGGT (SEQ ID NO: 23) eller CGCCTAGGTTGGGTAGGGTGGT-GGCG (SEQ ID No: 24), hvor nukleotidsekvensen til anvendelse som en aptamersekvens har en længde på højst 593 nukleotider, og II) produktion af en aptamer-oligonukleotid med nukleotidsekvensen opnået i trin I).
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Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14179715.9A EP2982756A1 (en) | 2014-08-04 | 2014-08-04 | Aptamers for use against autoantibody-associated diseases |
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EP3446714B1 (en) | 2011-06-02 | 2021-03-31 | University of Louisville Research Foundation, Inc. | Anti-nucleolin agent-conjugated nanoparticles |
EP2982756A1 (en) * | 2014-08-04 | 2016-02-10 | Berlin Cures Holding AG | Aptamers for use against autoantibody-associated diseases |
CN109451729B (zh) | 2016-06-08 | 2022-03-22 | 哈佛学院院长及董事 | 工程化病毒载体减少了炎症和免疫反应的诱导 |
WO2019094548A1 (en) | 2017-11-08 | 2019-05-16 | President And Fellows Of Harvard College | Compositions and methods for inhibiting viral vector-induced inflammatory responses |
WO2020086895A1 (en) * | 2018-10-24 | 2020-04-30 | Scivera LLC | Computer-implemented method for quantifying chemical hazard assessment |
EP3715374A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the sequestration of undesirable antibodies in a patient |
US11986536B2 (en) | 2019-03-23 | 2024-05-21 | Ablevia Biotech Gmbh | Compound for the sequestration of undesirable antibodies in a patient |
EP3715376A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the prevention or treatment of myasthenia gravis |
EP3715375A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the prevention or treatment of pre-eclampsia |
MX2023003375A (es) | 2020-09-23 | 2023-03-31 | Ablevia Biotech Gmbh | Compuesto para aumentar la eficacia de la terapia de sustitucion del factor viii. |
AU2021347583A1 (en) | 2020-09-23 | 2023-05-25 | Ablevia Biotech Gmbh | Compound for increasing efficacy of viral vectors |
EP4216990A1 (en) | 2020-09-23 | 2023-08-02 | Ablevia biotech GmbH | Compound for the sequestration of undesirable antibodies in a patient |
TW202228784A (zh) | 2020-09-23 | 2022-08-01 | 奧地利商艾柏力維亞生技有限公司 | 用以於一患者中螯合非預期的抗peg抗體的化合物 |
JP2023542389A (ja) | 2020-09-23 | 2023-10-06 | アブレヴィア バイオテック ゲーエムベーハー | 自己抗体で媒介される状態の予防又は治療のための化合物 |
KR20230074552A (ko) | 2020-09-24 | 2023-05-30 | 아블레비아 바이오테크 게엠베하 | 중증 근무력증의 예방 또는 치료용 화합물 |
CN113588937A (zh) * | 2021-07-19 | 2021-11-02 | 刘艳 | 一种心肌细胞m3受体的检测方法 |
CN114533889B (zh) * | 2022-02-25 | 2023-05-26 | 中南大学 | 一种DNA功能化PBNPs纳米酶制备方法和在靶向光热治疗剂制备中的应用 |
WO2023180502A1 (en) | 2022-03-24 | 2023-09-28 | Ablevia Biotech Gmbh | Compound for increasing efficacy of oncolytic viruses |
WO2024038918A1 (ja) * | 2022-08-19 | 2024-02-22 | 国立大学法人東京農工大学 | 一本鎖抗体結合アプタマー |
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AU2590799A (en) * | 1998-02-19 | 1999-09-06 | Ortho-Mcneil Pharmaceutical, Inc. | Azole peptidomimetics as thrombin receptor antagonists |
WO1999065928A2 (en) * | 1998-06-19 | 1999-12-23 | Genzyme Corporation | Polynucleotide population isolated from non-metastatic and metastatic breast tumor tissues |
ES2296615T3 (es) * | 1999-04-08 | 2008-05-01 | Antisoma Research Limited | Actividad antiproliferativa de oligonucleotidos ricos en g y procedimiento de uso de los mismos para su union a la nucleolina. |
WO2002068425A1 (en) * | 2001-02-23 | 2002-09-06 | Ortho-Mcneil Pharmaceutical, Inc. | Aminomethyl-pyrroloquinazoline compounds as thrombin receptor antagonists |
WO2005037323A2 (en) | 2003-10-10 | 2005-04-28 | University Of Louisville Research Foundation, Inc. | Use of gro to treat or prevent inflammation |
AU2006283025A1 (en) | 2005-08-26 | 2007-03-01 | Archemix Corp. | Aptamers that bind thrombin with high affinity |
US20090131351A1 (en) * | 2007-11-16 | 2009-05-21 | Antisoma Research Limited | Methods, compositions, and kits for modulating tumor cell proliferation |
WO2011133142A1 (en) * | 2010-04-20 | 2011-10-27 | University Of Louisville | Treatment of vhl-negative tumors |
EP2402016A1 (en) | 2010-06-29 | 2012-01-04 | Charité - Universitätsmedizin Berlin | Aptamers that inhibit interaction between antibody and 1st or 2nd extracellular loop of human beta-1-adrenergic receptor |
EP2497828A1 (en) * | 2011-03-07 | 2012-09-12 | Charité - Universitätsmedizin Berlin | Use of aptamers in therapy and/or diagnosis of autoimmune diseases |
EP2982756A1 (en) * | 2014-08-04 | 2016-02-10 | Berlin Cures Holding AG | Aptamers for use against autoantibody-associated diseases |
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CN117230073A (zh) | 2023-12-15 |
AU2015299059B2 (en) | 2017-08-03 |
JP2023022189A (ja) | 2023-02-14 |
CA2956877C (en) | 2019-06-25 |
JP2017529872A (ja) | 2017-10-12 |
BR112017002270A2 (pt) | 2018-01-16 |
PL3177723T3 (pl) | 2018-05-30 |
JP2018171070A (ja) | 2018-11-08 |
JP7267689B2 (ja) | 2023-05-02 |
WO2016020377A1 (en) | 2016-02-11 |
US20170226513A1 (en) | 2017-08-10 |
EP2982756A1 (en) | 2016-02-10 |
AU2015299059A1 (en) | 2017-03-02 |
CA2956877A1 (en) | 2016-02-11 |
EP3177723B1 (en) | 2017-12-06 |
CN117247941A (zh) | 2023-12-19 |
JP2021035369A (ja) | 2021-03-04 |
EP3177723A1 (en) | 2017-06-14 |
JP6630356B2 (ja) | 2020-01-15 |
ES2658492T3 (es) | 2018-03-12 |
CN106795516A (zh) | 2017-05-31 |
BR112017002270B1 (pt) | 2020-11-24 |
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