DK2524039T3 - Behandling af kønshormonbindende globulin- (shbg) relaterede sygdomme ved hæmning af naturligt antisense-transskript mod shbg - Google Patents
Behandling af kønshormonbindende globulin- (shbg) relaterede sygdomme ved hæmning af naturligt antisense-transskript mod shbg Download PDFInfo
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Claims (15)
1. Oligonukleotid, der er mälrettet et naturligt antisense-transskript fra konshormonbindende globulin (SHBG) til anvendelse som en terapeutisk forbindelse, hvor oligonukleotidet modulerer ekspressionen af konshormonbindende globulin (SHBG), og hvor: (a) det naturlige antisense-transskript har nukleinsyresekvensen ifolge SEQ ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3; eller (b) oligonukleotidet omfatter mindst én af SEQ ID NO: 4, 6 til 9 eller 11.
2. Oligonukleotid, der er mälrettet et naturligt antisense-transskript fra konshormonbindende globulin (SHBG) til anvendelse i forebyggelse eller behandling af en konshormonbindende globulin- (SHBG) forbundet sygdom eller forstyrrelse, hvor oligonukleotidet modulerer ekspressionen af konshormonbindende globulin (SHBG), og hvor: (a) det naturlige antisense-transskript har nukleinsyresekvensen ifolge SEQ ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3; eller (b) oligonukleotidet omfatter mindst én af SEQ ID NO: 4, 6 til 9 eller 11.
3. Anvendelse af et oligonukleotid, der er mälrettet et naturligt antisense-transskript fra konshormonbindende globulin (SHBG) til fremstilling af et medikament til forebyggelse eller behandling af en konshormonbindende globulin- (SHBG) associeret sygdom eller forstyrrelse, hvor oligonukleotidet modulerer ekspressionen af konshormonbindende globulin (SHBG), og hvor: (a) det naturlige antisense-transskript har nukleinsyresekvensen ifolge ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3; eller (b) oligonukleotidet omfatter mindst én af SEQ ID NO: 4, 6 til 9 eller 11.
4. Anvendelse ifolge krav 3, eller oligonukleotid til anvendelse ifolge krav 2, hvor sygdommen eller forstyrrelsen er udvalgt fra gruppen bestâende af alopeci, en sygdom eller forstyrrelse forbundet med abnorm funktion og/eller ekspression af SHBG, en neurologisk sygdom eller forstyrrelse, en psykologisk sygdom eller forstyrrelse (f.eks. humor- eller affektforstyrrelser, en hukommelsesdysfunktionssygdom eller -forstyrrelse, en amnestisk sygdom eller forstyrrelse, en motorisk og tic-forstyrrelse, stofmisbrugssygdom eller -forstyrrelse, en psykotisk sygdom eller forstyrrelse, en angstsygdom eller -forstyrrelse mv.j, en psykotisk sygdom eller forstyrrelse (f.eks. skizofreni, skizofreniform forstyrrelse, skizoaffektiv forstyrrelse og forstyrrelse med vrangforestilling, angstforstyrrelser, säsom panikforstyrrelse, fobier (indbefattende agorafobi), en obsessiv-kompulsiv forstyrrelse, posttraumatisk stressforstyrrelse etc.), en fertilitetssygdom eller -forstyrrelse, hirsutisme, en sygdom eller forstyrrelse forbundet med spermatogenese, en sygdom eller forstyrrelse forbundet med sædkvalitet, ovarieinsufficiens, en humorforstyrrelse (f.eks. minor og major dépréssion, dystymisk forstyrrelse, bipolare forstyrrelser og lignende), motorisk og tic-forstyrrelse (f.eks. Tourettes forstyrrelse, kronisk motor eller vokal tic-forstyrrelse, transient tic-forstyrrelse og stereotypisk bevægelsesforstyrrelse), Aspergers syndrom, en stofmisbrugsforstyrrelse (f.eks. stofafhængighed, stofmisbrug og folgevirkninger af stofmisbrug/afhængighed, sâsom stofinducerede psykologiske forstyrrelser, abstinenser og stofinduceret demens, amnestiske forstyrrelser mv.), en metabolisk sygdom eller forstyrrelse (f.eks. hypothyroidisme, en forstyrrelse forbundet med kronisk stress, symptomer forbundet med rygmarvslæsion, sâsom nedsat lungefunktion, oget colontransittid og lignende), en kronisk stressrelateret sygdom eller forstyrrelse (f.eks. kroniske stressrelaterede tilstande indbefatterfibromyalgi, kronisk træthedssyndrom, dysregulering af hypothalamus-hypofyseakse, kronisk sovnmangel og tilstande forbundet med forhojede niveauer af interleukin 6 (IL-6)), en sovnsygdom eller forstyrrelse, steroidafhængig cancer (f.eks. indbefattende prostatacancer og brystcancer, sâsom ostrogenreceptor positiv (ER+)), en konssygdom eller forstyrrelse eller dysfunktion, polycystisk ovariesyndrom, osteoporose, hyperinsulinæmi, glucoseintolerans, insulinresistens, en kardiovaskulær sygdom eller forstyrrelse og diabetes.
5. Fremgangsmâde in vitro til modulering af ekspressionen af konshormonbindende globulin (SHBG) i patientceller eller -væv, hvilken fremgangsmâde omfatter: etablering af kontakt mellem celler eller væv og et oligonukleotid, der er mälrettet et naturligt antisense-transskript fra konshormonbindende globulin (SHBG); hvorved ekspressionen af konshormonbindende globulin (SHBG) moduleres, og hvor: (a) det naturlige antisense-transskript har nukleinsyresekvensen ifolge SEQ ID NO: 3; eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3; eller (b) oligonukleotidet omfatter mindst én af SEQ ID NO: 4, 6 til 9 eller 11.
6. Anvendelse ifolge krav 3 eller 4, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2 eller 4, eller fremgangsmâde ifolge krav 5, hvor oligonukleotidet oger ekspressionen af konshormonbindende globulin (SHBG).
7. Anvendelse ifolge et hvilket som helst af kravene 3, 4 eller 6, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2,4 eller 6, eller fremgangsmâde ifolge krav 5 eller 6, hvor oligonukleotidet er enkeltstrenget.
8. Anvendelse ifolge et hvilket som helst af kravene 3, 4 eller 6, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2,4 eller 6, eller fremgangsmâde ifolge krav 5 eller 6, hvor oligonukleotidet er en siRNA-forbindelse.
9. Anvendelse ifolge et hvilket som helst af kravene 3, 4 eller 6 til 8, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2, 4 eller 6 til 8, eller fremgangsmâde ifolge et hvilket som helst af kravene 5 til 8, hvor det naturlige antisense-transskript har nukleinsyresekvensen ifolge SEQ ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3, og oligonukleotidet omfatter mindst én af SEQ ID NO: 12 til 17.
10. Anvendelse ifolge et hvilket som helst af kravene 3, 4 eller 6 til 9, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2,4, eller 6 til 9, eller fremgangsmâde ifolge et hvilket som helst af kravene 5 til 9, hvor ekspressionen af konshormonbindende globulin (SHBG) er oget med mindst 10%.
11. Anvendelse ifolge et hvilket som helst af kravene 3, 4 eller 6 til 10, eller oligonukleotid til anvendelse ifolge et hvilket som helst af kravene 1,2,4 eller 6 til 10 eller fremgangsmâde ifolge et hvilket som helst af kravene 5 til 10, hvor oligonukleotidet endvidere omfatter én eller fiere modifikationer, der omfatter: a. mindst én modificeret internukleosidbinding udvalgt fra: et phosphorthioat, alkylphosphonat, phosphordithioat, alkylphosphonthioat, phosphoramidat, carbamat, carbonat, en phosphattriester, et acetamidat, carboxymethylester og kombinationer deraf; b. mindst ét modificeret nukleotid udvalgt fra: en peptidnukleinsyre (PNA), en last nukleinsyre (LNA), en arabino-nukleinsyre, en analog, et dérivât og kombinationer deraf; eller c. mindst én modificeret sukkerdel udvalgt fra: en 2’-0-methoxyethylmodificeret sukkerdel, en 2’-methoxymodificeret sukkerdel, en 2’-0-alkylmodificeret sukkerdel, en bicyklisk sukkerdel, en 2’-fluordel og kombinationer deraf.
12. Oligonukleotid der: a. specifikt kan hybridisere til et naturligt antisense-transskript, der har nukleinsyresekvensen ifolge SEQ ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3; eller b. omfatter mindst én af SEQ ID NO: 4, 6 til 9 eller 11 ; hvor eventuelt oligonukleotidet er enkeltstrenget eller en siRNA-forbindelse.
13. Oligonukleotid ifolge krav 12, der omfatter mindst én af: (i) et oligonukleotid, der specifikt kan hybridisere til et naturligt antisense-transskript, der har nukleinsyresekvensen ifolge SEQ ID NO: 3, eller en variant deraf, der bevarer funktionen af det naturlige antisense-transskript ifolge SEQ ID NO: 3, og hvor oligonukleotidet omfatter mindst én af SEQ ID NO: 12 til 17; eller (ii) SEQ ID NO: 4, 6 til 9 eller 11 ; hvor eventuelt oligonukleotidet endvidere omfatter én eller fiere modifikationer, der omfatter: a. mindst én modificeret internukleosidbinding udvalgt fra: et phosphorthioat, alkylphosphonat, phosphordithioat, alkylphosphonthioat, phosphoramidat, carbamat, carbonat, en phosphattriester, et acetamidat, carboxymethylester og kombinationer deraf; b. mindst ét modificeret nukleotid udvalgt fra: en peptidnukleinsyre (PNA), en lâst nukleinsyre (LNA), en arabino-nukleinsyre, en analog, et dérivât og kombinationer deraf; eller c. mindst én modificeret sukkerdel udvalgt fra: en 2’-0-methoxyethylmodificeret sukkerdel, en 2’-methoxymodificeret sukkerdel, en 2’-0-alkylmodificeret sukkerdel, en bicyklisk sukkerdel, en 2’-fluordel og kombinationer deraf.
14. Oligonukleotid ifolge krav 12 eller 13, hvor oligonukleotidet er mellem 10 til 30 nukleotider langt.
15. Farmaceutisk sammensætning, der omfatter mindst ét oligonukleotid ifolge et hvilket som helst af kravene 12 til 14 og en farmaceutisk acceptabel excipiens.
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US29373910P | 2010-01-11 | 2010-01-11 | |
PCT/US2011/020768 WO2011085347A2 (en) | 2010-01-11 | 2011-01-11 | Treatment of sex hormone binding globulin (shbg) related diseases by inhibition of natural antisense transcript to shbg |
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DK2524039T3 true DK2524039T3 (da) | 2018-03-12 |
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US (2) | US9200277B2 (da) |
EP (1) | EP2524039B1 (da) |
JP (1) | JP6027893B2 (da) |
KR (1) | KR101854926B1 (da) |
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ES (1) | ES2664866T3 (da) |
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CA2786535A1 (en) | 2011-07-14 |
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CN102803493B (zh) | 2018-07-31 |
US20160046942A1 (en) | 2016-02-18 |
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CN102803493A (zh) | 2012-11-28 |
US9200277B2 (en) | 2015-12-01 |
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EP2524039B1 (en) | 2017-11-29 |
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