Compositions of TLR ligands and antivirals
The invention relates to methods and products for the treatment of viral infection using a combination of anti-viral agents and TLR ligands. The invention also relates to screening assays, associated products, kits, and in vitro methods.
1 . A composition comprising an immunostimulatory oligonucleotide and an anti-viral agent, wherein the anti-viral agent is not a C-8 substituted guanosine or an imidazoquinoline and wherein the anti-viral agent is linked to the immunostimulatory oligonucleotide.
2 . The composition of claim 1 , wherein the immunostimulatory oligonucleotide:
a) is linked to the anti-viral agent directly;
b) is linked to the anti-viral agent indirectly;
c) comprises a chimeric backbone;
d) an RNA oligonucleotide; or
e) a DNA oligonucleotide.
3 . (canceled)
4 . The composition of claim 2 a), wherein the immunostimulatory oligonucleotide and the anti-viral agent are part of the same molecule.
5 . The composition of claim 1 wherein the anti-viral agent is one or more nucleotide analogues.
6 . The composition of claim 2 a), further comprising a nuclease susceptible site between immunostimulatory oligonucleotide and the anti-viral agent.
7 . The composition of claim 2 a), wherein the immunostimulatory oligonucleotide contains at least one 3′-3′ linkage or at least one 5′-5′ linkage.
8 . (canceled)
9 . The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
10 .- 34 . (canceled)
35 . A composition of claim 2 d), wherein the anti-viral agent is associated with the immunostimulatory RNA oligonucleotide.
36 . The composition of claim 35 , wherein the immunostimulatory RNA oligonucleotide is:
a) linked to the anti-viral agent;
b) directly linked to the anti-viral agent; or
c) indirectly linked to the anti-viral agent.
37 .- 38 . (canceled)
39 . The composition of claim 36 a), wherein the immunostimulatory RNA oligonucleotide and the anti-viral agent are part of the same molecule.
40 . The composition of claim 35 , wherein the immunostimulatory RNA oligonucleotide is not linked to the anti-viral agent.
41 . The composition of claim 40 , wherein the composition includes
a) a microparticle housing the immunostimulatory RNA oligonucleotide and the anti-viral agent; or
b) a liposome housing the immunostimulatory RNA oligonucleotide and the anti-viral agent.
42 . (canceled)
43 . The composition of claim 35 , wherein the anti-viral agent is:
a) one or more nucleotide analogues; or
b) a C-8 substituted guanosine.
44 .- 47 . (canceled)
48 . The composition of claim 43 b), wherein the C-8 substituted guanosine is incorporated in the RNA oligonucleotide.
49 . The composition of claim 48 , wherein the C-8 substituted guanosine is positioned at the 5′ end of the RNA oligonucleotide.
50 . The composition of claim 48 , wherein the C-8 substituted guanosine is positioned one, two or three nucleotides 3′ of the 5′ end of the RNA oligonucleotide.
51 . A method for treating viral disease, comprising administering to a subject in need of such treatment a composition of claim 1 in an amount effective to treat the viral disease.
52 .- 73 . (canceled)
74 . A composition comprising a TLR7/8/9 ligand linked to an anti-viral agent.
75 . The composition of claim 74 , wherein the TLR7/8/9 ligand is an immunostimulatory oligonucleotide.
76 . The composition of claim 74 , wherein the TLR7/8/9 ligand is:
a) linked to the anti-viral agent directly; or
b) linked to the anti-viral agent indirectly.
77 . (canceled)
78 . The composition of claim 76 a), wherein the TLR7/8/9 ligand and the anti-viral agent are part of the same molecule.
79 . The composition of claim 74 wherein the anti-viral agent is one or more nucleotide analogues.
80 . The composition of claim 76 a), further comprising a nuclease susceptible site between the TLR7/8/9 ligand and the anti-viral agent.
81 .- 88 . (canceled)
89 . A method for treating bacterial infection comprising administering to a subject having a bacterial infection a composition of claim 1 in an amount effective to treat the bacterial infection.
90 . The method of claim 89 , wherein the anti-viral agent is linked to the immunostimulatory oligonucleotide.
91 . (canceled)
92 . The method of claim 89 , wherein the immunostimulatory oligonucleotide is:
a) an RNA oligonucleotide; or
b) a DNA oligonucleotide.
93 .- 102 . (canceled)
103 . The composition of claim 1 , wherein the immunostimulatory oligonucleotide is SEQ ID NO: 2 or SEQ ID NO: 12.
104 . The composition of claim 35 , wherein the immunostimulatory RNA oligonucleotide is SEQ ID NO: 2 or SEQ ID NO: 12.
105 . The method of claim Si, wherein the anti-viral agent is linked to the immunostimulatory oligonucleotide.
106 . The method of claim 51 , wherein the immunostimulatory oligonucleotide is:
a) an RNA oligonucleotide; or
b) a DNA oligonucleotide.
107 . The method of claim 104 a), wherein the immunostimulatory RNA oligonucleotide is SEQ ID NO: 2 or SEQ ID NO: 12.
108 . The method of claim 92 a), wherein the immunostimulatory RNA oligonucleotide is SEQ ID NO: 2 or SEQ ID NO: 12.