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US 8,796,239 B2Granted
Sirna compounds comprising terminal substitutions
AssigneeQuark Pharmaceuticals, Inc.
InventorSharon Avkin-Nachum
Life of this patent
Estimating the term…
Abstract
The invention relates to modified siRNA compounds which down-regulate target gene expression, to pharmaceutical compositions comprising such compounds and to methods of treating and/or preventing the incidence or severity of various diseases or conditions associated with the genes and/or symptoms associated with such diseases or conditions.
Claims18
A double-stranded nucleic acid having structure (A) set forth below:
- (A)
- 5′ N1-(N)x-Z
- 3′ (antisense strand)
- 3′ Z′-N2-(N′)y-z″
- 5′ (sense strand)
- wherein each of N2, N and N′ is an unmodified ribonucleotide, a modified ribonucleotide, or an unconventional moiety;
- wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the adjacent N or N′ by a covalent bond;
- wherein x=y=18;
- wherein the sequence of N2—(N′)y is fully complementary to the sequence of N1—(N)x and the sequence of (N)x has complementarity to a consecutive sequence in a target RNA;
- wherein N1 is covalently bound to (N)x and not complementary to the corresponding nucleotide in the target RNA or is an unconventional moiety complementary to the target RNA;
- wherein:
- N1 is selected from the group consisting of adenosine and deoxyadenosine when the corresponding nucleotide in the target RNA sequence is adenosine;
- or
- N1 is selected from the group consisting of adenosine, deoxyadenosine and deoxythymidine when the corresponding nucleotide in the target RNA sequence is cytidine;
- or
- N1 is selected from the group consisting of adenosine, deoxyadenosine and deoxythymidine when the corresponding nucleotide in the target RNA sequence is guanosine;
- or
- N1 is selected from the group consisting of uridine and deoxyuridine when the corresponding nucleotide in the target RNA sequence is uridine;
- wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′ terminus of N2—(N′)y;
- and
- wherein each of Z and Z′ is independently present or absent, but if present is independently 1-5 consecutive nucleotides, 1-5 consecutive non-nucleotide moieties or a combination of 1-5 nucleotides and non-nucleotide moieties, covalently attached at the 3′ terminus of the strand in which it is present;
- or a pharmaceutically acceptable salt of the double stranded nucleic acid.
19 more elements
A double-stranded nucleic acid having structure (A) set forth below:
- (A)
- 5′ N1-(N)x-Z
- 3′ (antisense strand)
- 3′ Z′-N2-(N′)y-z″
- 5′ (sense strand)
- wherein each of N2, N and N′ is an unmodified ribonucleotide, a modified ribonucleotide, or an unconventional moiety;
- wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the adjacent N or N′ by a covalent bond;
- wherein x=y=18;
- wherein the sequence of N2—(N′)y is fully complementary to the sequence of N1—(N)x and the sequence of (N)x has complementarity to a consecutive sequence in a target RNA;
- wherein N1 is covalently bound to (N)x and not complementary to the corresponding nucleotide in the target RNA or is an unconventional moiety complementary to the target RNA;
- wherein N1 is selected from the group consisting of adenosine and deoxyadenosine, and the corresponding nucleotide in the target RNA is adenosine;
- wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′ terminus of N2—(N′)y;
- and
- wherein each of Z and Z′ is independently present or absent, but if present is independently 1-5 consecutive nucleotides, 1-5 consecutive non-nucleotide moieties or a combination of 1-5 nucleotides and non-nucleotide moieties, covalently attached at the 3′ terminus of the strand in which it is present;
- or a pharmaceutically acceptable salt of the double stranded nucleic acid.
12 more elements
Dependencies are inferred from the claim text.