DK2513310T3 - Behandling af sygdomme forbundet med membranbundet transskriptionsfaktorpeptidase, sted 1 (mbtps1), ved hæmning af naturlig antisense-transskript til mbtps1 - Google Patents

Behandling af sygdomme forbundet med membranbundet transskriptionsfaktorpeptidase, sted 1 (mbtps1), ved hæmning af naturlig antisense-transskript til mbtps1 Download PDF

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DK2513310T3
DK2513310T3 DK10842521.6T DK10842521T DK2513310T3 DK 2513310 T3 DK2513310 T3 DK 2513310T3 DK 10842521 T DK10842521 T DK 10842521T DK 2513310 T3 DK2513310 T3 DK 2513310T3
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oligonucleotide
mbtps1
nucleic acid
antisense
rna
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Joseph Collard
Sherman Olga Khorkova
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Curna Inc
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Claims (15)

1. Oligonukleotid, der er målrettet et naturligt antisense-transskript af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), til anvendelse som en terapeutisk forbindelse, hvor oligonukleotidet øger ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1); hvor det naturlige antisense-transskript har nukleinsyresekvensen ifølge SEQ ID NO: 2, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifølge SEQ ID NO: 2.
2. Oligonukleotid, der er målrettet et naturligt antisense-transskript af en membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), til anvendelse i forebyggelse eller behandling af en sygdom eller forstyrrelse forbundet med membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), hvor oligonukleotidet øger ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), hvor sygdommen eller forstyrrelsen er udvalgt fra gruppen bestående af en sygdom eller forstyrrelse forbundet med ER-stressrespons, en inflammatorisk tarmsygdom (f.eks. colitis), en endochondral knogleudviklingssygdom eller forstyrrelse (f.eks. chondrodysplasi, chondrocyt-apoptose, desorganiseret kollagennetværk), og hvor det naturlige antisense-transskript har nukleinsyresekvensen ifølge SEQ ID NO: 2, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifølge SEQ ID NO: 2.
3. Anvendelse af et oligonukleotid, der er målrettet et naturligt antisense-transskript af en membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1) til fremstilling af et medikament til forebyggelse eller behandling af en sygdom eller forstyrrelse forbundet med en membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), hvor oligonukleotidet øger ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1), hvor sygdommen eller forstyrrelsen er udvalgt fra gruppen bestående af en sygdom eller forstyrrelse forbundet med ER-stressrespons, en inflammatorisk tarmsygdom (f.eks. colitis), en endochondral knogleudviklingssygdom eller forstyrrelse (f.eks. chondrodysplasi, chondrocyt-apoptose, desorganiseret kollagennetværk), og hvor det naturlige antisense-transskript har nukleinsyresekvensen ifølge SEQ ID NO: 2, eller en variant deraf der bevarer funktionen af det naturlige antisense-transskript ifølge SEQ ID NO: 2.
4. Fremgangsmåde in vitro til øgning af ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1) i patientceller eller -væv, der omfatter: etablering af kontakt mellem cellerne eller vævet og et oligonukleotid, der er målrettet et naturligt antisense-transskript af en membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1); hvorved ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1) øges; hvor det naturlige antisense-transskript har nukleinsyresekvensen ifølge SEQ ID NO: 2, eller en variant deraf der bevarer funktionen af det naturlige antisense-transskript ifølge SEQ ID NO: 2.
5. Anvendelse ifølge krav 3, eller et oligonukleotid til anvendelse ifølge krav 1 eller 2, eller fremgangsmåde ifølge krav 4, hvor oligonukleotidet er enkeltstregnet.
6. Anvendelse ifølge krav 3, eller et oligonukleotid til anvendelse ifølge krav 1 eller 2, eller fremgangsmåde ifølge krav 4, hvor oligonukleotidet er en siRNA-forbindelse.
7. Anvendelse ifølge et hvilket som helst af kravene 3, 5 eller 6, eller oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 1, 2, 5 eller 6, eller fremgangsmåde ifølge et hvilket som helst af kravene 4 til 6, hvor oligonukleotidet omfatter mindst én af SEQ ID NO: 3, 4 eller 6.
8. Anvendelse ifølge et hvilket som helst af kravene 3 eller 5 til 7, eller oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 1, 2 eller 5 til 7, eller fremgangsmåde ifølge et hvilket som helst af kravene 4 til 7, hvor ekspressionen af membranbundet transskriptionsfaktor-peptidase, sted 1 (MBTPS1) øges med mindst 10 %.
9. Anvendelse ifølge et hvilket som helst af kravene 3 eller 5 til 8, eller oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 1, 2 eller 5 til 8 eller fremgangsmåde ifølge et hvilket som helst af kravene 4 til 8, hvor oligonukleotidet endvidere omfatter én eller flere modifikationer, der omfatter: a. mindst én modificeret intemukleosidbinding udvalgt fra: et phosphorthioat, alkylphosphonat, phosphordithioat, alkylphosphonthioat, phosphoramidat, carbamat, carbonat, phosphattriester, acetamidat, en carboxymethylester og kombinationer deraf; b. mindst ét modificeret nukleotid udvalgt fra: en peptidnukleinsyre (PNA), en låst nukleinsyre (LNA), en arabino-nukleinsyre, en analog, et derivat og kombinationer deraf; eller c. mindst én modificeret sukkerdel udvalgt fra: en 2’-0-methoxyethyl-modificeret sukkerdel, en 2’-methoxy-modificeret sukkerdel, en 2’-0-alkyl-modificeret sukkerdel, en bicyklisk sukkerdel, en 2’-fluordel og kombinationer deraf
10. Oligonukleotid, der specifikt kan hybridiseres til et naturligt antisense-transskript, der har nukleinsyresekvens ifølge SEQ ID NO: 2, eller en variant deraf der bevarer funktionen af det naturlige antisense-transskript ifølge SEQ ID NO: 2.
11. Oligonukleotid, der omfatter mindst én af SEQ ID NO: 3, 4 eller 6.
12. Oligonukleotid ifølge krav 10 eller 11, hvor oligonukleotidet er enkeltstrenget eller en siRNA forbindelse.
13. Oligonukleotid ifølge et hvilket som helst af kravene 10 til 12, der endvidere omfatter én eller flere modifikationer, der omfatter: a. mindst én modificeret intemukleosidbinding udvalgt fra: et phosphorthioat, alkylphosphonat, phosphordithioat, alkylphosphonthioat, phosphoramidat, carbamat, carbonat, phosphattriester, acetamidat, en carboxymethylester og kombinationer deraf; b. mindst ét modificeret nukleotid udvalgt fra: en peptidnukleinsyre (PNA), en låst nukleinsyre (LNA), en arabino-nukleinsyre, en analog, et derivat og kombinationer deraf; eller c. mindst én modificeret sukkerdel udvalgt fra: en 2’-0-methoxyethyl modificeret sukkerdel, en 2’-methoxy-modificeret sukkerdel, en 2’-0-alkyl-modificeret sukkerdel, en bicyklisk sukkerdel, en 2’-fluordel og kombinationer deraf.
14. Oligonukleotid ifølge et hvilket som helst af kravene 10 til 13, hvor oligonukleotidet er mellem 10 til 30 nukleotider langt.
15. Farmaceutisk sammensætning, der omfatter mindst ét oligonukleotid ifølge et hvilket som helst af kravene 10 til 14 og en farmaceutisk acceptabel excipiens.
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