HRP20210315T1 - Oligonukleotidi za smanjenje ekspresije pd-l1 - Google Patents

Oligonukleotidi za smanjenje ekspresije pd-l1 Download PDF

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HRP20210315T1
HRP20210315T1 HRP20210315TT HRP20210315T HRP20210315T1 HR P20210315 T1 HRP20210315 T1 HR P20210315T1 HR P20210315T T HRP20210315T T HR P20210315TT HR P20210315 T HRP20210315 T HR P20210315T HR P20210315 T1 HRP20210315 T1 HR P20210315T1
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Croatia
Prior art keywords
oligonucleotide
pharmaceutical preparation
antisense oligonucleotide
oligonucleotide conjugate
antidirectional
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HRP20210315TT
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English (en)
Inventor
Lykke PEDERSEN
Hassan Javabakht
Malene JACKEROTT
Søren OTTOSEN
Souphalone LUANGSAY
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F. Hoffmann - La Roche Ag
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Application filed by F. Hoffmann - La Roche Ag filed Critical F. Hoffmann - La Roche Ag
Publication of HRP20210315T1 publication Critical patent/HRP20210315T1/hr

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Claims (20)

1. Protusmjerni oligonukleotid, naznačen time, da ima formulu [image] 1. , pri čemu velika slova predstavljaju nukleozide beta-D-oksi „rigidne“ nukleinske kiseline LNA, mala slova predstavljaju nukleozide DNA, sve LNA C su 5-metil citozin, a sve internukleozidne veze su fosforotioatne internukleozidne veze.
2. Protusmjerni oligonukleotidni konjugat, naznačen time, da sadrži oligonukleotid u skladu s patentnim zahtjevom 1 i konjugiranu skupinu koja je kovalentno vezana za spomenuti oligonukleotid.
3. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 2, naznačen time, da je prisutna spona između oligonukleotida i konjugirane skupine.
4. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 2 ili patentnim zahtjevom 3, naznačen time, da je konjugirana skupina ciljna skupina asijaloglikoproteinskog receptora.
5. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 4, naznačen time, da je ciljna skupina asijaloglikoproteinskog receptora trovalentna N- acetilgalaktozaminska (GalNAc) skupina.
6. Protusmjerni oligonukleotidni konjugat prema bilo kojem od patentnih zahtjeva 3 do 5, naznačen time, da je spona fiziološki labilna spona.
7. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 6, naznačen time, da je fiziološki labilna spona nukleazno osjetljiva spona.
8. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 6 ili 7, naznačen time, da fiziološki labilna spona sadrži citidin-adenozin dinukleotid.
9. Protusmjerni oligonukleotidni konjugat u skladu s patentnim zahtjevom 2, naznačen time, da je između oligonukleotida i konjugatne skupine prisutna spona; nadalje konjugirana skupina sadrži asijaloglikoproteinski receptor s ciljnom skupinom koja je trovalentna N-acetilgalaktozaminska (GalNAc) skupina; gdje je spona fiziološki labilna spona; nadalje fiziološki labilna spona sadrži citidin-adenozin dinukleotid.
10. Farmaceutski pripravak naznačen time, da sadrži protusmjerni oligonukleotid u skladu s patentnim zahtjevom 1 ili protusmjerni oligonukleotidni konjugat u skladu s bilo kojim od patentnih zahtjeva 2 do 9 i farmaceutski prihvatljivi razrjeđivač, otapalo, nosač, sol i/ili adjuvans.
11. Farmaceutski pripravak u skladu s patentnim zahtjevom 10, naznačen time, da je farmaceutski prihvatljivi razrjeđivač sterilna fiziološka otopina puferirana s fosfatom.
12. Farmaceutski pripravak u skladu s patentnim zahtjevom 10 ili 11, naznačen time, da je farmaceutski prihvatljiva sol natrij.
13. Farmaceutski pripravak u skladu s patentnim zahtjevom 10 ili 11, naznačen time, da je farmaceutski prihvatljiva sol kalij.
14. In vitro postupak za moduliranje ekspresije PD-L1 u ciljnoj stanici koja eksprimira PD-L1, spomenuti postupak koji obuhvaća primjenu na spomenutu stanicu protusmjernog oligonukleotida iz patentnog zahtjeva 1, protusmjernog oligonukleotidnog konjugata iz bilo kojeg od patentnih zahtjeva 2 do 9 ili farmaceutskog pripravka iz bilo kojeg od patentnih zahtjeva 10 do 13 u učinkovitoj količini.
15. Protusmjerni oligonukleotid u skladu s patentnim zahtjevom 1, protusmjerni oligonukleotidni konjugat u skladu s bilo kojim od patentnih zahtjeva 2 do 9 ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 10 do 13, naznačeni time, da su za uporabu u obnavljanju imunološkog odgovora na virus.
16. Protusmjerni oligonukleotid, protusmjerni oligonukleotidni konjugat ili farmaceutski pripravak za uporabu u skladu s patentnim zahtjevom 15, naznačen time, da je virus HBV.
17. Protusmjerni oligonukleotid u skladu s patentnim zahtjevom 1, protusmjerni oligonukleotidni konjugat u skladu s bilo kojim od patentnih zahtjeva 2 do 9 ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 10 do 13, naznačeni time, da su za uporabu u obnavljanju imunološkog odgovora na parazita.
18. Protusmjerni oligonukleotid, protusmjerni oligonukleotidni konjugat ili farmaceutski pripravak za uporabu u skladu s bilo kojim od patentnih zahtjeva 15 do 16, naznačeni time, da obnavljanje imunološkog odgovora predstavlja povećanje CD8+ T stanica u jetri specifičnih za jedan ili više HBV antigena u usporedbi s kontrolom.
19. Protusmjerni oligonukleotid u skladu s patentnim zahtjevom 1, protusmjerni oligonukleotidni konjugat u skladu s bilo kojim od patentnih zahtjeva 2 do 9 ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 10 do 13, naznačeni time, da se koriste kao lijek.
20. Protusmjerni oligonukleotid u skladu s patentnim zahtjevom 1, protusmjerni oligonukleotidni konjugat u skladu s bilo kojim od patentnih zahtjeva 2 do 9 ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 10 do 13, naznačeni time, da su za uporabu u liječenju HBV infekcije.
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