NUCLEIC ACIDS COMPRISING FORMULA (NuGlXmGnNv)a AND DERIVATIVES THEREOF AS IMMUNOSTIMULATING AGENT/ADJUVANT
The present invention relates to nucleic acids of the general formula (I): (N u G l X m G n N v ) a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N u G l X m G n N v ) a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.
1 - 25 . (canceled)
26 . An isolated nucleic acid molecule comprising at least 100 contagious nucleotides of SEQ ID NO: 114-119 or the DNA coding sequence thereof, provided that:
the guanosine (guanine), the uridine (uracil), the adenosine (adenine), the thymidine (thymine), or the cytidine (cytosine) positions of the nucleotide (nucleoside) sequence of the nucleic acid molecule may be substituted with an analogue of nucleotides (nucleosides) selected from 1-methyl-adenosine (adenine), 2-methyl-adenosine (adenine), 2-methylthio-N6-isopentenyl-adenosine (adenine), N6-methyl-adenosine (adenine), N6-isopentenyl-adenosine (adenine), 2-thio-cytidine (cytosine), 3-methyl-cytidine (cytosine), 4-acetyl-cytidine (cytosine), 2,6-diaminopurine, 1-methyl-guanosine (guanine), 2-methyl-guanosine (guanine), 2,2-dimethyl-guanosine (guanine), 7-methyl-guanosine (guanine), inosine, 1-methyl-inosine, dihydro-uridine (uracil), 4-thio-uridine (uracil), 5-carboxymethylaminomethyl-2-thio-uridine (uracil), 5-(carboxyhydroxylmethyl)-uridine (uracil), 5-fluoro-uridine (uracil), 5-bromo-uridine (uracil), 5-carboxymethylaminomethyl-uridine (uracil), 5-methyl-2-thio-uridine (uracil), N-uridine (uracil)-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uridine (uracil), 5-methoxyaminomethyl-2-thio-uridine (uracil), 5′-methoxycarbonylmethyl-uridine (uracil), 5-methoxy-uridine (uracil), uridine (uracil)-5-oxyacetic acid methyl ester, uridine (uracil)-5-oxyacetic acid (v), queosine, beta-D-mannosyl-queosine, wybutoxosine, and inosine;
phosphate moieties may be substituted with phosphoramidates, phosphorothioates, peptide nucleotides, or methylphosphonates; and
ribose components may be substituted with deoxyribose.
27 . The isolated nucleic acid molecule of claim 26 , comprising at least 150 contagious nucleotides of SEQ ID NO: 114-119.
28 . The isolated nucleic acid molecule of claim 27 , comprising at least 200 contagious nucleotides of SEQ ID NO: 114-119.
29 . The isolated nucleic acid molecule of claim 26 , comprising at least 200 contagious nucleotides of SEQ ID NO: 114-116.
30 . The isolated nucleic acid molecule of claim 29 , comprising at least 200 contagious nucleotides of SEQ ID NO: 114.
31 . The isolated nucleic acid molecule of claim 30 , comprising the sequence of SEQ ID NO: 114.
32 . The isolated nucleic acid molecule of claim 26 , comprising at least 200 contagious nucleotides of SEQ ID NO: 117-119.
33 . The isolated nucleic acid molecule of claim 32 , comprising at least 200 contagious nucleotides of SEQ ID NO: 117.
34 . The isolated nucleic acid molecule of claim 33 , comprising the sequence of SEQ ID NO: 117.
35 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule is RNA.
36 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule is single-stranded.
37 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule is double-stranded or partially double-stranded.
38 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule is linear.
39 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule is complexed with a lipid, polycationic compound, or polycationic polypeptide.
40 . The isolated nucleic acid molecule of claim 26 , wherein the nucleic acid molecule does not comprise a nucleoside analogue.
41 . The isolated nucleic acid molecule of claim 26 , comprising at least 200 contagious nucleotides of SEQ ID NO: 114-119 or the DNA coding sequence thereof, provided that:
the guanosine (guanine), the uridine (uracil), the adenosine (adenine), the thymidine (thymine), or the cytidine (cytosine) positions of the nucleotide (nucleoside) sequence of the nucleic acid molecule may be substituted with an analogue of nucleotides (nucleosides) selected from 1-methyl-adenosine (adenine), 2-methyl-adenosine (adenine), 2-methylthio-N6-isopentenyl-adenosine (adenine), N6-methyl-adenosine (adenine), N6-isopentenyl-adenosine (adenine), 2-thio-cytidine (cytosine), 3-methyl-cytidine (cytosine), 4-acetyl-cytidine (cytosine), 2,6-diaminopurine, 1-methyl-guanosine (guanine), 2-methyl-guanosine (guanine), 2,2-dimethyl-guanosine (guanine), 7-methyl-guanosine (guanine), inosine, 1-methyl-inosine, dihydro-uridine (uracil), 4-thio-uridine (uracil), 5-carboxymethylaminomethyl-2-thio-uridine (uracil), 5-(carboxyhydroxylmethyl)-uridine (uracil), 5-fluoro-uridine (uracil), 5-bromo-uridine (uracil), 5-carboxymethylaminomethyl-uridine (uracil), 5-methyl-2-thio-uridine (uracil), N-uridine (uracil)-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uridine (uracil), 5-methoxyaminomethyl-2-thio-uridine (uracil), 5′-methoxycarbonylmethyl-uridine (uracil), 5-methoxy-uridine (uracil), uridine (uracil)-5-oxyacetic acid methyl ester, uridine (uracil)-5-oxyacetic acid (v), queosine, beta-D-mannosyl-queosine, wybutoxosine, and inosine;
phosphate moieties may be substituted with phosphoramidates, phosphorothioates, peptide nucleotides, or methylphosphonates; and
ribose components may be substituted with deoxyribose.
42 . The isolated nucleic acid molecule of claim 41 , wherein the nucleic acid molecules is RNA.
43 . The isolated nucleic acid molecule of claim 41 , wherein the nucleic acid molecule does not comprise a nucleoside analogue.
44 . A pharmaceutical composition comprising the nucleic acid molecule according to claim 26 and a pharmaceutically acceptable carrier.
45 . The pharmaceutical composition of claim 44 , further comprising an adjuvant.
46 . The pharmaceutical composition of claim 44 , further comprising an antigen.
47 . The pharmaceutical composition of claim 44 , wherein the antigen is a RNA encoding polypeptide antigen.
48 . The pharmaceutical composition of claim 44 , wherein the antigen is a polypeptide antigen.