IMMUNOSTIMULATORY NUCLEIC ACID PACKAGED PARTICLES FOR THE TREATMENT OF HYPERSENSITIVITY
The application is related to compositions and methods for the treatment of hypersensitivity, wherein the compositions comprise a particle packaged with immunostimulatory nucleic acids. The compositions of the invention are particularly useful in the treatment of atopic eczema, asthma and IgE-mediated allergy (type I allergy), especially pollen allergy and house dust allergy.
1 . A method of treating hypersensitivity in an animal, wherein said hypersensitivity is allergy or asthma, wherein said method comprises introducing a composition into said animal, and wherein said composition comprises:
(a) a virus-like particle of an RNA bacteriophage; and
(b) an unmethylated CpG-containing oligonucleotide;
wherein said virus-like particle of an RNA bacteriophage is packaged with said unmethylated CpG-containing oligonucleotide, and wherein said method does not comprise co-administering an allergen to said animal, and wherein introduction of said composition treats said hypersensitivity in said animal.
2 - 6 . (canceled)
7 . The method of claim 1 , wherein said virus-like particle of an RNA bacteriophage comprises coat proteins, or fragments thereof, of an RNA bacteriophage.
8 . The method of claim 1 , wherein said RNA bacteriophage is selected from the group consisting of:
(a) bacteriophage Qβ;
(b) bacteriophage R17;
(c) bacteriophage fr;
(d) bacteriophage GA;
(e) bacteriophage SP;
(f) bacteriophage MS2;
(g) bacteriophage M11;
(h) bacteriophage MX1;
(i) bacteriophage NL95;
(j) bacteriophage f2;
(k) bacteriophage PP7; and
(l) bacteriophage AP205.
9 - 19 . (canceled)
20 . The method of claim 1 , wherein said unmethylated CpG containing oligonucleotide is capable of stimulating IFN-alpha production in a cell.
21 - 24 . (canceled)
25 . The method of claim 1 , wherein said unmethylated CpG-containing oligonucleotide comprises a palindromic sequence.
26 . The method of claim 1 , wherein the CpG motif of said unmethylated CpG-containing oligonucleotide is part of a palindromic sequence.
27 . The method of claim 26 , wherein said palindromic sequence is GACGATCGTC (SEQ ID NO:28).
28 . The method of claim 25 , wherein said palindromic sequence is flanked at its 5′-terminus and at its 3′-terminus by guanosine entities.
29 . The method of claim 25 , wherein said palindromic sequence is flanked at its 5′-terminus by at least 3 and at most 15 guanosine entities, and wherein said palindromic sequence is flanked at its 3′-terminus by at least 3 and at most 15 guanosine entities.
30 . The method of claim 1 , wherein said unmethylated CpG-containing oligonucleotide comprises the sequence selected from the group consisting of:
(SEQ ID NO: 32)
(a) “G6-6” GGGGGGGACGATCGTCGGGGGG;
(SEQ ID NO: 33)
(b) “G7-7” GGGGGGGGACGATCGTCGGGGGGG;
(SEQ ID NO: 25)
(c) “G8-8” GGGGGGGGGACGATCGTCGGGGGGGG;
(SEQ ID NO: 26)
(d) “G9-9” GGGGGGGGGGACGATCGTCGGGGGGGGG;
and
(SEQ ID NO: 27)
(e) “G10” GGGGGGGGGGGACGATCGTCGGGGGGGGGG.
31 . The method of claim 1 , wherein said unmethylated CpG-containing oligonucleotide comprises the sequence
(SEQ ID NO: 27)
GGGGGGGGGG GACGATCGTC GGGGGGGGGG.
32 . The method of claim 1 , wherein said unmethylated CpG-containing oligonucleotide consists exclusively of phosphodiester bound nucleotides.
33 - 39 . (canceled)
40 . The method of claim 1 , wherein said hypersensitivity is asthma.
41 . The method of claim 40 , wherein said asthma is IgE-mediated asthma.
42 - 53 . (canceled)
54 . The method of claim 1 , wherein said animal is a human.
55 . (canceled)
56 . (canceled)
57 . The method of claim 1 , wherein said method does not comprise introducing to said animal.
58 . (canceled)
59 . (canceled)
60 . The method of claim 1 wherein an allergen is not introduced in said animal for at least one week before and at least one week after said introduction of said composition in said animal.
61 . (canceled)
62 . The method of claim 1 , wherein an allergen is not introduced in said animal for at least eight weeks before and at least eights weeks after said introduction of said composition in said animal.
63 - 79 . (canceled)
80 . The method of claim 1 , wherein said virus-like particle of an RNA bacteriophage essentially consists of coat proteins having the amino acid sequence of SEQ ID NO:3.
81 . The method of claim 1 , wherein said composition does not comprise an allergen.