US2010316659A1PendingUtilityA1
Immunostimulatory oligoribonucleotides
Est. expiryNov 25, 2025(expired)· nominal 20-yr term from priority
A61P 31/04A61P 31/20A61P 31/12A61P 31/00A61P 35/00A61P 37/04A61P 37/06A61P 31/14A61P 37/08A61P 43/00A61P 37/02A61P 11/06A61K 2039/55561A61K 31/7105C12N 2310/17A61K 39/39C12N 15/117C12N 2310/315A61K 9/127
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Claims
Abstract
The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
Claims
exact text as granted — not AI-modified1 - 75 . (canceled)
76 . An oligoribonucleotide selected from the group consisting of
UUAGGCAC;
(SEQ ID NO: 2)
AUAGGCC;
SEQ ID NO: 4
GCCACCGAGCCGAAUAUACC;
SEQ ID NO: 11
AUAUAUAUAUAUAUAUAUAU;
SEQ ID NO: 12
AAUAAUAAUAAUAAUAAUAA;
SEQ ID NO: 16
AAAUAAAUAAAUAAAUAAAU;
SEQ ID NO: 17
AAAAUAAAAUAAAAUAAAAU;
SEQ ID NO: 18
CUACUACUACUACUACUACU;
SEQ ID NO: 24
UUAUUAU;
SEQ ID NO: 30
UAUAUAU;
SEQ ID NO: 33
CCGAGCCGCCGCCCCC;
SEQ ID NO: 35
CCGAGCCGCAUAUCCC;
SEQ ID NO: 36
CCGAGCCGCUAUACCC;
SEQ ID NO: 37
CCGAGCCAUAUAUCCC;
SEQ ID NO: 38
CCGAGCCAUAUAUAUC;
SEQ ID NO: 39
CCGAGCCGAAUAACCC;
SEQ ID NO: 40
CCGAGCCGCAUAACCC;
SEQ ID NO: 41
CCGAGCCGAAUACCCC;
SEQ ID NO: 42
CCGAGCCGCCUAACCC;
SEQ ID NO: 43
CCGAGCCGAAUCCCCC;
SEQ ID NO: 44
CCGAGCCGCAUACCCC;
SEQ ID NO: 45
CCGAGCCGCAUCCCCC;
SEQ ID NO: 46
CCGAGCCGCCUACCCC;
SEQ ID NO: 47
CCGAGCCGCAUUACCC;
SEQ ID NO: 48
CCGAGCCGCUAUCCCC;
SEQ ID NO: 55
CCGAGCCGAAGGCACC;
SEQ ID NO: 56
CCGAGCCGAAUGUACC;
SEQ ID NO: 63
CCGAGCCGAUAUUACC;
SEQ ID NO: 65
CCGAGCCGAUUGAACC;
SEQ ID NO: 76
CCGAGCCGAAGGUACC;
SEQ ID NO: 82
CCGAGCCGAAGGUGCC;
SEQ ID NO: 83
CCGAGCCGAAGCUCCC;
SEQ ID NO: 84
CCGAGCCGAAGAUACC;
SEQ ID NO: 85
CCGAGCCGAAGCUACC;
SEQ ID NO: 87
and
CCGAGCCGAAGCUGCC;
SEQ ID NO: 88
and wherein the oligoribonucleotide includes at least one backbone modification.
77 . The oligoribonucleotide of claim 76 , wherein the oligoribonucleotide is complexed to N-[1-(2,3-Dioleoyloxy)propyl],N,N,N-trimethylammonium methyl-sulfate to form a conjugate.
78 . The oligoribonucleotide of claim 76 wherein the backbone comprises internucleotide phosphorothioate linkages between each nucleotide.
79 . The oligoribonucleotide of claim 76 , wherein the oligoribonucleotide is separated from a 5′ ribonucleotide by a non-nucleotide linker.
80 . The oligoribonucleotide of claim 76 , wherein the oligoribonucleotide is separated from a 3′ ribonucleotide by a non-nucleotide linker.
81 . The oligoribonucleotide of claim 76 , wherein the oligoribonucleotide is separated from a 5′ and 3′ ribonucleotide by a non-nucleotide linker.
82 . A composition comprising an oligoribonucleotide selected from the group consisting of
UUAGGCAC;
SEQ ID NO: 2
AUAGGCC;
SEQ ID NO: 4
GCCACCGAGCCGAAUAUACC;
SEQ ID NO: 11
AUAUAUAUAUAUAUAUAUAU;
SEQ ID NO: 12
AAUAAUAAUAAUAAUAAUAA;
SEQ ID NO: 16
AAAUAAAUAAAUAAAUAAAU;
SEQ ID NO: 17
AAAAUAAAAUAAAAUAAAAU;
SEQ ID NO: 18
CUACUACUACUACUACUACU;
SEQ ID NO: 24
UUAUUAU;
SEQ ID NO: 30
UAUAUAU;
SEQ ID NO: 33
CCGAGCCGCCGCCCCC;
SEQ ID NO: 35
CCGAGCCGCAUAUCCC;
SEQ ID NO: 36
CCGAGCCGCUAUACCC;
SEQ ID NO: 37
CCGAGCCAUAUAUCCC;
SEQ ID NO: 38
CCGAGCCAUAUAUAUC;
SEQ ID NO: 39
CCGAGCCGAAUAACCC;
SEQ ID NO: 40
CCGAGCCGCAUAACCC;
SEQ ID NO: 41
CCGAGCCGAAUACCCC;
SEQ ID NO: 42
CCGAGCCGCCUAACCC;
SEQ ID NO: 43
CCGAGCCGAAUCCCCC;
SEQ ID NO: 44
CCGAGCCGCAUACCCC;
SEQ ID NO: 45
CCGAGCCGCAUCCCCC;
SEQ ID NO: 46
CCGAGCCGCCUACCCC;
SEQ ID NO: 47
CCGAGCCGCAUUACCC;
SEQ ID NO: 48
CCGAGCCGCUAUCCCC
SEQ ID NO: 55
CCGAGCCGAAGGCACC;
SEQ ID NO: 56
CCGAGCCGAAUGUACC;
SEQ ID NO: 63
CCGAGCCGAUAUUACC;
SEQ ID NO: 65
CCGAGCCGAUUGAACC;
SEQ ID NO: 76
CCGAGCCGAAGGUACC;
SEQ ID NO: 82
CCGAGCCGAAGGUGCC;
SEQ ID NO: 83
CCGAGCCGAAGCUCCC;
SEQ ID NO: 84
CCGAGCCGAAGAUACC;
SEQ ID NO: 85
CCGAGCCGAAGCUACC;
SEQ ID NO: 87
and
CCGAGCCGAAGCUGCC;
SEQ ID NO: 88
in a delivery vehicle, wherein said oligoribonucleotide includes at least one backbone modification; and optionally non-nucleotidic linkers; and optionally a) lipophilic moiety, b) CpG motif, c) antigen, d) adjuvant, and e) pharmaceutically acceptable carrier.
83 . The composition of claim 82 wherein the delivery vehicle is N-[2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate.
84 . The composition of claim 82 further comprising a lipophilic moiety.
85 . The composition of claim 82 wherein the lipohilic moiety and the oligoribonucleotide are conjugated.
86 . The composition of claim 82 further comprising a CpG motif.
87 . The composition of claim 82 further comprising an antigen.
88 . The composition of claim 82 further comprising an adjuvant.
89 . A method for modulating an immune response in a subject, comprising administering to a subject in need thereof an oligoribonucleotide of claim 76 in an effective amount to modulate an immune response.
90 . The method of claim 89 , wherein the oligoribonucleotide is delivered by a route selected from the group consisting of oral, nasal, sublingual, intravenous, subcutaneous, mucosal, respiratory, direct injection, and dermally.Join the waitlist — get patent alerts
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