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NZ744548B2 - Oligonucleotides for reduction of pd-l1 expression - Google Patents
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NZ744548B2 - Oligonucleotides for reduction of pd-l1 expression - Google Patents

Oligonucleotides for reduction of pd-l1 expression Download PDF

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Publication number
NZ744548B2
NZ744548B2 NZ744548A NZ74454817A NZ744548B2 NZ 744548 B2 NZ744548 B2 NZ 744548B2 NZ 744548 A NZ744548 A NZ 744548A NZ 74454817 A NZ74454817 A NZ 74454817A NZ 744548 B2 NZ744548 B2 NZ 744548B2
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NZ
New Zealand
Prior art keywords
conjugate
antisense oligonucleotide
moiety
linker
oligonucleotide conjugate
Prior art date
Application number
NZ744548A
Other versions
NZ744548A (en
Inventor
Malene Jackerott
Hassan Javanbakht
Souphalone Luangsay
S Ren Ottosen
Lykke Pedersen
Original Assignee
F Hoffmann La Roche Ag
Filing date
Publication date
Application filed by F Hoffmann La Roche Ag filed Critical F Hoffmann La Roche Ag
Priority claimed from PCT/EP2017/055925 external-priority patent/WO2017157899A1/en
Publication of NZ744548A publication Critical patent/NZ744548A/en
Publication of NZ744548B2 publication Critical patent/NZ744548B2/en

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    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
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    • C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
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    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
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Abstract

The present invention relates to antisense oligonucleotides that are capable of reducing expression of PD-L1 in a target cell. The oligonucleotides hybridize to PD-L1 mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of viral liver infections such as HBV, HCV and HDV; a parasite infections such as malaria, toxoplasmosis, leishmaniasis and trypanosomiasis or liver cancer or metastases in the liver using the oligonucleotide.

Claims (10)

1. An antisense oligonucleotide of formula CCtatttaacatcAGAC, wherein capital letters represent beta-D-oxy LNA nucleosides, lowercase letters represent DNA nucleosides, all LNA C are 5-methyl cytosine and all internucleoside linkages are phosphorothioate internucleoside linkages.
2. An antisense oligonucleotide conjugate comprising the oligonucleotide of claim 1 and a conjugate moiety covalently attached to said oligonucleotide.
3. The antisense oligonucleotide conjugate of claim 2, wherein a linker is present between the oligonucleotide and the conjugate moiety.
4. The antisense oligonucleotide conjugate of claim 2 or claim 3, wherein the conjugate moiety is an asialoglycoprotein receptor targeting moiety.
5. The antisense oligonucleotide conjugate of claim 4, wherein the asialoglycoprotein receptor targeting moiety is a tri-valent N-acetylgalactosamine (GalNAc) moiety.
6. The antisense oligonucleotide conjugate of any one of claims 3 to 5, wherein the linker is a physiologically labile linker.
7. The antisense oligonucleotide conjugate of claim 6, wherein the physiologically labile linker is a nuclease susceptible linker.
8. The antisense oligonucleotide conjugate of claim 6 or claim 7, wherein the physiologically labile linker comprises a cytidine-adenosine dinucleotide.
9. The antisense oligonucleotide conjugate of claim 2, wherein a linker is present between the oligonucleotide and the conjugate moiety; further wherein the conjugate moiety comprises an asialoglycoprotein receptor targeting moiety that is a tri-valent N-acetylgalactosamine (GalNAc) moiety; wherein the linker is a physiologically labile linker; further wherein the physiologically labile linker comprises a cytidine-adenosine dinucleotide.
10. The antisense oligonucleotide conjugate of any one of claims 2 to 9, wherein the antisense oligonucleotide conjugate is of formula GN2-C6ocoaoCCtatttaacatcAGAC, wherein C6 represents an amino alkyl group with 6 carbons, capital letters represent beta-D-oxy LNA nucleosides, lowercase letters represent DNA nucleosides, all LNA C are 5-methyl cytosine, subscript o represent a phosphodiester nucleoside linkage and, unless otherwise indicated, all internucleoside linkages are phosphorothioate internucleoside linkages, and wherein GN2 represents the trivalent GalNAc cluster shown in
NZ744548A 2017-03-14 Oligonucleotides for reduction of pd-l1 expression NZ744548B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16160149 2016-03-14
PCT/EP2017/055925 WO2017157899A1 (en) 2016-03-14 2017-03-14 Oligonucleotides for reduction of pd-l1 expression

Publications (2)

Publication Number Publication Date
NZ744548A NZ744548A (en) 2024-05-31
NZ744548B2 true NZ744548B2 (en) 2024-09-03

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