Immunostimulatory, Covalently lipidated oligonucleotides
AssigneeBiomira, 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.
Claims100
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, and
- (2) at least one covalently incorporated lipophilic group.
(canceled)
An immunostimulatory molecule which comprises at least one oligonucleotide strand, said strand comprising a nucleotide sequence, the 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, and
- (2) at least one covalently incorporated lipophilic group,
- where the number of nucleotides in said strand is less than eight.
An immunostimulatory molecule which comprises (I) 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, and
- (2) at least one covalently incorporated lipophilic group, and
- (II) an epitope.
(canceled)
An immunostimulatory molecule which comprises (I) at least one oligonucleotide strand which comprises
- (1) at least one nucleotide sequence comprising a plurality of nucleotides, each nucleotide comprising a nucleoside, each nucleoside comprising a nucleobase, each nucleoside being joined to at least one other nucleoside by an internucleoside linkage,
- said molecule comprising two or more segments, each segment consisting of nucleosides joined to each other by short internucleoside linkages, each segment being joined to at least one other segment by a long internucleoside linkage,
- at least two of said segments each comprising at least one CxG dinucleotide unit or analogue thereof, and
- (2) at least one covalently incorporated lipophilic group.
An immunostimulatory molecule which comprises at least one oligonucleotide strand, said strand comprising
- (1) a nucleotide sequence, the 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, and
- (2) at least one covalently incorporated lipophilic group,
- where said nucleotide sequence comprises at least one pair of adjacent thymine nucleobases which are dimerized to form a thymine dimer.
Dependencies are inferred from the claim text.