Nucleic acid compounds
AssigneeTangram Therapeutics PLC
InventorsAmy MCCARTHY, Graham CRAGGS, James LONGDEN, Ines DE SANTIAGO, Duncan BROWN, Ahmad Ali MORTAZAVI, Viviana MANNELLA, Muthusamy JAYARAMAN, Alexandre DEBACKER, Adrian James MOGG
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Abstract
The present invention provides novel nucleic acid compound suitable for therapeutic use. Additionally, the present invention provides methods of making these compounds, as well as methods of using such compounds for the treatment of various diseases and conditions.
Claims85
A nucleic acid for inhibiting expression of B4GALT1, comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is:
- (i) at least partially complementary to a portion of RNA transcribed from the B4GALT1 gene, and
- (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand sequences as listed in Table 2.
A nucleic acid for inhibiting expression of B4GALT1, comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is:
- (i) at least partially complementary to a portion of RNA transcribed from the B4GALT1 gene, and
- (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand modified sequences as listed in Table 3.
A nucleic acid according to any preceding claim, wherein the first strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 23 nucleosides.
A nucleic acid according to any preceding claim, wherein the second strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 21 nucleosides.
A nucleic acid according to any preceding claim, wherein the duplex region of the nucleic acid is between 17 and 30 nucleosides in length, more preferably is 19 or 21 nucleosides in length.
A nucleic acid according to any preceding claim, wherein the region of complementarity between the first strand and the portion of RNA transcribed from the B4GALT1 gene is between 17 and 30 nucleosides in length.
A nucleic acid according to any preceding claim, wherein the nucleic acid is either blunt ended, or comprises one or more single-stranded nucleoside overhangs, optionally wherein the overhang is present on the first or second strand, preferably at the 3′ terminus of the first or second strand, and/or wherein the overhang comprises 1 to 4 nucleosides, more preferably 2 nucleosides.
A nucleic acid according to any preceding claim, wherein the nucleic acid is an siRNA oligonucleoside.
A nucleic acid according to any preceding claim, wherein one or more nucleosides on the first and/or second strand are modified, to form modified nucleosides.
A nucleic acid according to any preceding claim, which further comprises one or more abasic nucleosides, optionally wherein the one or more abasic nucleosides are in a terminal region of the second strand, and/or wherein at least one abasic nucleoside is linked to an adjacent basic nucleoside through a reversed internucleoside linkage.
A nucleic acid according to any preceding claim, wherein the nucleic acid comprises one or more phosphorothioate internucleoside linkages.
A nucleic acid according to any preceding claim, wherein the nucleic acid is conjugated directly or indirectly to one or more ligand moieties, optionally wherein said ligand moiety is present at a terminal region of the second strand, preferably at the 3′ terminal region thereof.
A pharmaceutical composition comprising a nucleic acid according to any preceding claim, in combination with a pharmaceutically acceptable excipient or carrier.
A nucleic acid or pharmaceutical composition according to any preceding claim, for use in therapy.
A nucleic acid or pharmaceutical composition according to any preceding claim, for use in prevention or treatment of diabetes.
A nucleic acid or pharmaceutical composition according to any preceding claim, for use in prevention or treatment of cardiovascular disease.
Dependencies are inferred from the claim text.