Immunostimulatory, covalently lipidated oligonucleotides
AssigneeOncothyreon Inc.
InventorsZi-Hua Jiang, Rao Koganty, Damayanthi Yalamati, Myung-Gi Baek
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Abstract
Covalently lipidated oligonucleotides comprising the CpG dinucleotide unit, or an analogue thereof, may be used as immunostimulatory agents to protect against a disease caused by a cancer cell or a pathogen, either alone or in conjunction with immunogens and/or non-immunological agents. Lipidated oligonucleotides with special backbones, lipidated oligonucleotides with fewer than eight nucleotides, and lipidated oligonucleotides comprising a plurality of CpG dinucleotide-containing segments connected by a long internucleoside linkage are of particular interest. These compounds are also novel per se.
Claims89
A method of stimulating the immune system of a subject which comprises administering to the subject an immunologically effective amount of an isolated immunostimulatory molecule which comprises at least one oligonucleotide strand which comprises
- (1) at least one nucleotide sequence comprising a plurality of nucleotides, each nucleotide comprising a nucleobase, and thereby also comprising at least one CxG dinucleotide unit or analogue thereof,
- in which there are no more than six nucleobases in each oligonucleotide strand,
- wherein in said analogue, (1) cytosine is replaced with a cytosine analogue which is a pyrimidine other than thymine or uracil, and/or (2) guanine is replaced with a guanine analogue which is a purine other than adenine, and
- (2) at least one covalently incorporated lipophilic group.
A method of stimulating the immune system of a subject which comprises administering to the subject an immunologically effective amount of an immunostimulatory molecule which comprises at least one oligonucleotide strand which comprises
- (1) at least one nucleotide sequence comprising a plurality of nucleotides, each nucleotide comprising a nucleobase, and thereby also comprising at least one CxG dinucleotide unit or analogue thereof,
- in which there are no more than six nucleobases in each oligonucleotide strand,
- wherein in said analogue, (1) cytosine is replaced with a cytosine analogue which is a pyrimidine other than thymine or uracil, and/or (2) guanine is replaced with a guanine analogue which is a purine other than adenine, and
- (2) at least one covalently incorporated lipophilic group.
Dependencies are inferred from the claim text.