Oligonucleotides for treatment of angiopoietin like 4 (ANGPTL4) related diseases
AssigneeEmpirico Inc.
InventorsOmri Gottesman, Shannon Bruse, Brian Cajes, David Lewis, David Rozema
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Abstract
Provided are compositions comprising an oligonucleotide that targets Angiopoietin-like 4 (ANGPTL4). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating a metabolic or cardiovascular disorder by providing an oligonucleotide that targets ANGPTL4 to a subject in need thereof.
Claims20
A composition comprising an oligonucleotide that targets Angiopoietin like 4 (ANGPTL4) and when administered to a cell decreases expression of ANGPTL4;
- wherein the oligonucleotide comprises a small interfering RNA (siRNA) comprising a sense strand and an antisense strand, wherein the sense strand comprises an oligonucleotide sequence of any of SEQ ID NOS:
- 13971-13973 or 13975-13977 in which at least one internucleoside linkage is modified and at least one nucleoside is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside substitutions, additions, or deletions of any of 13971-13973 or 13975-13977 in which at least one internucleoside linkage is modified and at least one nucleoside is modified;
- and wherein the antisense strand comprises an oligonucleotide sequence of any of SEQ ID NOS:
- 13979-13981 or 13983-13985 in which at least one internucleoside linkage is modified and at least one nucleoside is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside substitutions, additions, or deletions of any of SEQ ID NOS:
- 13979-13981 or 13983-13985 in which at least one internucleoside linkage is modified and at least one nucleoside is modified.
A composition comprising an oligonucleotide that targets Angiopoietin like 4 (ANGPTL4) and when administered to a cell decreases expression of ANGPTL4;
- wherein the oligonucleotide comprises a small interfering RNA (siRNA) comprising a sense strand and an antisense strand, wherein the sense strand comprises an oligonucleotide sequence of any of SEQ ID NOS:
- 13970-13977 in which at least one internucleoside linkage is modified and at least one nucleoside is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside substitutions, additions, or deletions of any of SEQ ID NOS:
- 13970-13977 in which at least one internucleoside linkage is modified and at least one nucleoside is modified;
- wherein the antisense strand comprises an oligonucleotide sequence of any of SEQ ID NOS:
- 13978-13985 in which at least one internucleoside linkage is modified and at least one nucleoside is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside substitutions, additions, or deletions of any of SEQ ID NOS:
- 13978-13985 in which at least one internucleoside linkage is modified and at least one nucleoside is modified;
- and
- wherein the sense strand or the antisense strand comprises one of the following modification patterns:
- 5′-NfsnsNfnNfnNfNfNfnNfnNfnNfnNfnNfsnsn-3′ (SEQ ID NO:
- 13954), 5′-nsnsnnNfnNfNfNfnnnnnnnnnnsnsn-3′ (SEQ ID NO:
- 13955), 5′-nsnsnnNfnNfnNfnnnnnnnnnnsnsn-3′ (SEQ ID NO:
- 13956), 5′-NfsnsNfnNfnNfNfNfnNfnNfnNfnNfnNfsnsnN-3′ (SEQ ID NO:
- 13957), 5′-nsnsnnNfnNfNfNfnnnnnnnnnnsnsnN-3′ (SEQ ID NO:
- 13958), 5′-NfsnsNfnNfnNfnNfnNfnNfnNfnNfnNfsnsn-3′ (SEQ ID NO:
- 13959), 5′-nsNfsnNfnNfnNfnNfnnnNfnNfnNfnsnsn-3′ (SEQ ID NO:
- 13960), 5′-nsNfsnnnNfnNfNfnnnnNfnNfnnnsnsn-3′ (SEQ ID NO:
- 13961), 5′-nsNfsnnnNfnnnnnnnNfnNfnnnsnsn-3′ (SEQ ID NO:
- 13962), 5′-nsNfsnNfnNfnnnnnnnNfnNfnnnsnsn-3′ (SEQ ID NO:
- 13963), 5′-nsNfsnnnNfnNfnnnnnNfnNfnnnsnsn-3′ (SEQ ID NO:
- 13964), 5′-nsNfsnNfnNfnNfnNfnNfnNfnNfnNfnsnsn-3′ (SEQ ID NO:
- 13965), 5′-nsNfsnNfnNfnNfNfnnnnNfnNfnnnsnsn-3′ (SEQ ID NO:
- 13966), 5′-nsNfsnnnnnnnnnnnNfnnnnnsnsn-3′ (SEQ ID NO:
- 13967), or 5′-nsNfsnnnNfnnnnnnnNfnNfnNfnsnsn-3′ (SEQ ID NO:
- 13968), wherein “N” comprises one or more nucleosides, “Nf” is a 2′ fluoro-modified nucleoside, “n” is a 2′ O-methyl modified nucleoside, and “s” is a phosphorothioate linkage.
Dependencies are inferred from the claim text.