Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsGunther Hartmann, Antonin Fougerolles, Veit Hornung, Stefan Endres
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Abstract
This invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.
Claims27
A method of stimulating an immune response in a mammal comprising the step of administering to said mammal an oligonucleotide agent consisting of, consisting essentially of, or comprising a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, preferably taken from the 5′ end of this sequence.
A method of making an oligonucleotide agent so as to avoid stimulating an immune response in a mammal comprising the step of eliminating from a potential agent pool any agent that comprises a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, preferably taken from the 5′ end of this sequence, or a sequence that differs from SEQ ID NO:1 by not more than one or not more than 2 nucleotides.
An isolated oligonucleotide agent for inducing an immune response consisting of, consisting essentially of, or comprising a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, preferably taken from the 5′ end of this sequence.
A method of making an oligonucleotide agent so as to induce an immune response in a mammal, comprising the step of adding to a potential agent pool any agent that comprises 4 or more, 5 or more, 6 or more, 7 or more, or 8 or more contiguous nucleotides of SEQ ID NO:1, or a sequence that differs from SEQ ID NO:1 by not more than one or not more than 2 nucleotides.
A method of concomitantly inhibiting the expression of a gene and inducing an immune response in a mammal, comprising administering to said mammal an iRNA agent comprising a sequence of 4 or more, 5 or more, 6 or more, 7 or more, or 8 or more contiguous nucleotides of SEQ ID NO:1, preferably taken from the 5′ end of this sequence, or a sequence that differs from SEQ ID NO:1 by not more than one or not more than 2 nucleotides.
A method of evaluating an iRNA agent comprising:
- a. providing a candidate iRNA agent;
- b. reviewing the candidate iRNA agent to determine if it includes SEQ ID NO:1 or a sequence that differs from SEQ ID NO:1 by 1 or 2 nucleotides.
A method of making an oligonucleotide agent so as to avoid stimulating an immune response in a mammal, wherein said oligonucleotides comprises a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, comprising providing the oligonucleotide agent in such manner that it contains at least 2, or at least 4,2′-O-methyl modified nucleotides.
Dependencies are inferred from the claim text.