US2020085942A1PendingUtilityA1
NUCLEIC ACIDS COMPRISING FORMULA (NuGlXmGnNv)a AND DERIVATIVES THEREOF AS IMMUNOSTIMULATING AGENT/ADJUVANT
Est. expiryJan 31, 2028(~1.5 yrs left)· nominal 20-yr term from priority
A61P 37/08A61P 35/04A61P 37/02A61P 37/06A61P 3/10A61P 37/04A61P 33/00A61P 29/00A61P 31/18A61P 31/04A61P 31/16A61P 31/12A61P 31/06A61P 33/12A61P 31/20A61P 31/22A61P 27/16A61P 33/10A61P 33/02A61P 35/02A61P 33/14A61P 33/06A61P 31/00A61P 31/08A61P 27/02A61P 35/00A61P 31/14A61P 25/00A61P 33/04A61P 31/10A61P 17/14C12N 15/117C12N 2310/17A61P 11/02A61K 2039/55561A61K 2039/572A61P 1/04A61P 1/16C12N 2310/315C07H 21/00A61K 2039/53A61P 17/06A61K 39/39A61P 21/04A61P 17/00A61P 19/02C12N 2310/314A61P 17/04A61P 11/06C12N 2320/31Y02A50/30
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Claims
Abstract
The present invention relates to nucleic acids of the general formula (I): (NuGlXmGnNv)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): (NuGlXmGnNv)a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.
Claims
exact text as granted — not AI-modified1 . Nucleic acid molecule of formula (I):
(N u G l X m G n N v ) a , wherein: G is guanosine, uridine or an analogue of guanosine or uridine; X is guanosine, uridine, adenosine, thymidine, cytidine, or an analogue of these nucleotides; N is a nucleic acid sequence having a length of about 4 to 50, each N independently selected from from guanosine, uridine, adenosine, thymidine, cytidine or an analogue of these nucleotides; a is an integer from 1 to 20; l is an integer from 1 to 40,
wherein when l=1, G is guanosine or an analogue thereof,
when l>1, at least 50% of these nucleotides are guanosine or an analogue thereof;
m is an integer and is at least 3;
wherein when m=3, X is uridine or an analogue thereof, and
when m>3, at least 3 successive uridines or analogues of uridine occur;
n is an integer from 1 to 40,
wherein when n=1, G is guanosine or an analogue thereof,
when n>1, at least 50% of these nucleotides are guanosine or an analogue thereof;
u, v may be independently from each other an integer from 0 to 50;
wherein the nucleic acid molecule of formula (I) has a length of at least 50 nucleotides, nucleotides and wherein X m contains a monotonic uracil sequence having a length of at least 8 uridines or uracil analogues.
2 . Nucleic acid according to claim 1 , characterized in that the nucleic acid molecule of formula (I) contains a core structure G l X m G n , selected from at least one sequence according to any of SEQ ID NOs: 1-5, 10-18, 23-31, 36-53, 59-66 and 71-79:
(SEQ ID NO: 1)
GGUUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 2)
GGGGGUUUUUUUUUUGGGGG;
(SEQ ID NO: 3)
GGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGG;
(SEQ ID NO: 4)
GUGUGUGUGUGUUUUUUUUUUUUUUUUGUGUGUGUGUGU;
(SEQ ID NO: 5)
GGUUGGUUGGUUUUUUUUUUUUUUUUUGGUUGGUUGGUU;
(SEQ ID NO: 10)
GGGGGGUUUUUUUUGGGGGG;
(SEQ ID NO: 11)
GGGGGGUUUUUUUUUGGGGG;
(SEQ ID NO: 12)
GGGGGGUUUUUUUUUUGGGG;
(SEQ ID NO: 13)
GGGGGUUUUUUUUUUUGGGG;
(SEQ ID NO: 14)
GGGGGUUUUUUUUUUUUGGG;
(SEQ ID NO: 15)
GGGGUUUUUUUUUUUUUGGG;
(SEQ ID NO: 16)
GGGGUUUUUUUUUUUUUUGG;
(SEQ ID NO: 17)
GGUUUUUUUUUUUUUUUUGG;
(SEQ ID NO: 18)
GUUUUUUUUUUUUUUUUUUG;
(SEQ ID NO: 23)
GGGGGGGUUUUUUUUGGGGGGG;
(SEQ ID NO: 24)
GGGGGGGUUUUUUUUUGGGGGG;
(SEQ ID NO: 25)
GGGGGGGUUUUUUUUUUGGGGG;
(SEQ ID NO: 26)
GGGGGGUUUUUUUUUUUGGGGG;
(SEQ ID NO: 27)
GGGGGGUUUUUUUUUUUUGGGG;
(SEQ ID NO: 28)
GGGGGUUUUUUUUUUUUUGGGG;
(SEQ ID NO: 29)
GGGGGUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 30)
GGGUUUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 31)
GGUUUUUUUUUUUUUUUUUUGG;
(SEQ ID NO: 36)
GGGGGGGUUUUUUUUGGGGGGGG;
(SEQ ID NO: 37)
GGGGGGGUUUUUUUUUGGGGGGG;
(SEQ ID NO: 38)
GGGGGGGUUUUUUUUUUGGGGGG;
(SEQ ID NO: 39)
GGGGGGUUUUUUUUUUUGGGGGG;
(SEQ ID NO: 40)
GGGGGGUUUUUUUUUUUUGGGGG;
(SEQ ID NO: 41)
GGGGGUUUUUUUUUUUUUGGGGG;
(SEQ ID NO: 42)
GGGGGUUUUUUUUUUUUUUGGGG;
(SEQ ID NO: 43)
GGGUUUUUUUUUUUUUUUUGGGG;
(SEQ ID NO: 44)
GGGUUUUUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 45)
GUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUG;
(SEQ ID NO: 46)
GGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGG;
(SEQ ID NO: 47)
GGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 48)
GGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGG;
(SEQ ID NO: 49)
GGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGG;
(SEQ ID NO: 50)
GGGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGG;
(SEQ ID NO: 51)
GGGGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGGG;
(SEQ ID NO: 52)
GGGGGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGGGG;
(SEQ ID NO: 53)
GGGGGGGGGUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGGGGG;
(SEQ ID NO: 59)
GGUUUUUUUUGG;
(SEQ ID NO: 60)
GGUUUUUUUUUGG;
(SEQ ID NO: 61)
GGUUUUUUUUUUGG;
(SEQ ID NO: 62)
GGUUUUUUUUUUUGG;
(SEQ ID NO: 63)
GGUUUUUUUUUUUUGG;
(SEQ ID NO: 64)
GGUUUUUUUUUUUUUGG;
(SEQ ID NO: 65)
GGUUUUUUUUUUUUUUGG;
(SEQ ID NO: 66)
GGUUUUUUUUUUUUUUUGG;
(SEQ ID NO: 71)
GGGUUUUUUUGGG;
(SEQ ID NO: 72)
GGGUUUUUUUUGGG;
(SEQ ID NO: 73)
GGGUUUUUUUUUGGG;
(SEQ ID NO: 74)
GGGUUUUUUUUUUGGG;
(SEQ ID NO: 75)
GGGUUUUUUUUUUUGGG;
(SEQ ID NO: 76)
GGGUUUUUUUUUUUUGGG;
(SEQ ID NO: 77)
GGGUUUUUUUUUUUUUGGG;
(SEQ ID NO: 78)
GGGUUUUUUUUUUUUUUUGGGUUUUUUUUUUUUUUUGGGUUUUUUUUU
UUUUUUGGG;
3 . Nucleic acid according to claim 1 , characterized in that the nucleic acid comprises the specific formula (II)
poly(X) s (N u G l X m G n N v ) a poly(X) t , wherein G, X, N, a, l, m, n, u and v are as defined above for formula (I); and poly(X) is a homopolymeric stretch of nucleic acids, wherein X may be any nucleic acid as defined for X of the nucleic acid molecule according to formula (I); and s, t is each an integer selected, independent from each other, from about 5 to 100,
wherein the nucleic acid molecule of formula (II) has a length of at least 50 nucleotides.
4 . Nucleic acid according to claim 3 , characterized in that the nucleic acid molecule according to formula (II) is specifically a nucleic acid molecule according to formula (IIa):
poly(X)(N u G l X m G n N v ) a
5 . Nucleic acid according to claim 3 , characterized in that the nucleic acid molecule according to formula (II) is specifically a nucleic acid molecule according to formula (IIb):
poly(X)(N u G l X m G n N v ) a poly(X)
6 . Nucleic acid according to claim 3 , characterized in that the homopolymeric stretch of nucleic acids poly(X) is a single-stranded, a partially double-stranded or a double-stranded RNA sequence.
7 . Nucleic acid according to claim 1 , characterized in that the homopolymeric stretch of nucleic acids poly(X) is selected from a single-stranded stretch of cytidines (poly(C)), guanosines (poly(G)), adenosines (poly(A)), uridines (poly(U)), inosines (poly(I)), or from a homopolymeric double-stranded stretch of inosines and cytoines (poly(I:C)), or of adenosines and uridines (poly(A:U)).
8 . Nucleic acid according to claim 3 , characterized in that the nucleic acid comprises the specific formula (IIIa):
(N u stem1G l X m G n stem2N v ) a , or the specific formula (IIIb):
(N u G l X m G n N v ) a stem1N w1 stem2N w2 ,
wherein each G, X, N, a, l, m, n, u and v is as defined above for formula (I); and w1, w2 are integers and independently of each other as defined above for integers u, v of formula (I); and stem1, stem2 are palindromic sequences and form a stem loop structure, wherein the palindromic sequences are each formed by a nucleic acid sequence having a length of about 5 to 50 nucleic acids, selected from adenosine, guanosine, cytidine, uridine, thymidine, or an anologue thereof.
9 . Nucleic acid according to claim 1 , characterized in that the nucleic acid molecule of formula (I), (II), (IIa), (IIb), (IIIa) and/or (IIIb) is in the form of RNA or DNA, is single-stranded, double-stranded or partially double-stranded, and/or is linear or circular.
10 . Nucleic acid according to claim 1 , characterized in that the nucleic acid of any of formula (I), (II), (IIa), (IIb), (IIIa) and/or (IIIb) is in the form of a single-stranded RNA, a double-stranded RNA or a or a partially double-stranded RNA, preferably a partially double-stranded RNA.
11 . Nucleic acid according to claim 1 , characterized in that the nucleic acid of any of formula (I), (II), (IIa), (IIb), (IIIa) and/or (IIIb) is present in the form of RNA and additionally has at the 5′ terminus a “Cap structure” and/or at the 3′ terminus a poly-A tail and/or at the 3′ terminus a poly-C tail.
12 . Nucleic acid according to claim 1 , characterized in that the nucleic acid is prepared by an in vitro translation.
13 . An immunostimulating agent comprising a nucleic acid of claim 1 .
14 . Pharmaceutical composition containing a nucleic acid according to claim 1 , a pharmaceutically acceptable carrier and, optionally, further auxiliary substances, additives and/or adjuvants.
15 . Pharmaceutical composition according to claim 14 , additionally comprising at least one pharmaceutically active component.
16 . Pharmaceutical composition according to claim 15 , characterized in that the at least one pharmaceutically active component is selected from the group consisting of peptides, proteins, nucleic acids, (therapeutically active) low molecular weight organic or inorganic compounds having a molecular weight less than 5000, sugars, antigens, antibodies, pathogens, attenuated pathogens, de-activated pathogens, (human) cells, cellular fragments or fractions and other therapeutic agents, which are preferably adapted to exhibit enhanced transfection properties, including by complexation with lipids and/or polycationic compounds, including polycationis peptides.
17 . Pharmaceutical composition according to claim 1 , characterized in that the composition contains at least one further adjuvant, which is an immunostimulating agent, selected from the group consisting of cationic peptides, including polypeptides including protamine, nucleoline, spermine or spermidine, cationic polysaccharides, including chitosan, TDM, MDP, muramyl dipeptide, pluronics, alum solution, aluminium hydroxide, ADJUMER™ (polyphosphazene); aluminium phosphate gel; glucans from algae; algammulin; aluminium hydroxide gel (alum); highly protein-adsorbing aluminium hydroxide gel; low viscosity aluminium hydroxide gel; AF or SPT (emulsion of squalane (5%), Tween 80 (0.2%), Pluronic L121 (1.25%), phosphate-buffered saline, pH 7.4); AVRIDINE™ (propanediamine); BAY R1005™ ((N-(2-deoxy-2-L-leucylamino-b-D-glucopyranosyl)-N-octadecyldodecanoyl-amide hydroacetate); CALCITRIOL™ (1-alpha,25-dihydroxy-vitamin D3); calcium phosphate gel; CAP™ (calcium phosphate nanoparticles); cholera holotoxin, cholera-toxin-A1-protein-A-D-fragment fusion protein, sub-unit B of the cholera toxin; CRL 1005 (block copolymer P1205); cytokine-containing liposomes; DDA (dimethyldioctadecylammonium bromide); DHEA (dehydroepiandrosterone); DMPC (dimyristoylphosphatidylcholine); DMPG (dimyristoylphosphatidylglycerol); DOC/alum complex (deoxycholic acid sodium salt); Freund's complete adjuvant; Freund's incomplete adjuvant; gamma inulin; Gerbu adjuvant (mixture of: i) N-acetylglucosaminyl-(P1-4)-N-acetylmuramyl-L-alanyl-D-glutamine (GMDP), ii) dimethyldioctadecylammonium chloride (DDA), iii) zinc-L-proline salt complex (ZnPro-8); GM-CSF); GMDP (N-acetylglucosaminyl-(b1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine); imiquimod (1-(2-methypropyl)-1H-imidazo[4,5-c]quinoline-4-amine); ImmTher™ (N-acetylglucosaminyl-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-glycerol dipalmitate); DRVs (immunoliposomes prepared from dehydration-rehydration vesicles); interferon-gamma; interleukin-1beta; interleukin-2; interleukin-7; interleukin-12; ISCOMS™ (“Immunostimulating Complexes”); ISCOPREP 7.0.3.™; liposomes; LOXORIBINE™ (7-allyl-8-oxoguanosine (guanine)); LT oral adjuvant ( E. coli labile enterotoxin-protoxin); microspheres and microparticles of any composition; MF59™; (squalene-water emulsion); MONTANIDE ISA 51™ (purified incomplete Freund's adjuvant); MONTANIDE ISA720™ (metabolisable oil adjuvant); MPL™ (3-Q-desacyl-4′-monophosphoryl lipid A); MTP-PE and MTP-PE liposomes ((N-acetyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1,2-dipalmitoyl-sn-glycero-3-(hydroxyphosphoryloxy))ethylamide, monosodium salt); MURAMETIDE™ (Nac-Mur-L-Ala-D-Gln-OCH 3 ); MURAPALMITINE™ and D-MURAPALMITINE™ (Nac-Mur-L-Thr-D-isoGln-sn-glyceroldipalmitoyl); NAGO (neuraminidase-galactose oxidase); nanospheres or nanoparticles of any composition; NISVs (non-ionic surfactant vesicles); PLEURAN™ (beta-glucan); PLGA, PGA and PLA (homo- and co-polymers of lactic acid and glycolic acid; microspheres/nanospheres); PLURONIC L121™; PMMA (polymethyl methacrylate); PODDS™ (proteinoid microspheres); polyethylene carbamate derivatives; poly-rA: poly-rU (polyadenylic acid-polyuridylic acid complex); polysorbate 80 (Tween 80); protein cochleates (Avanti Polar Lipids, Inc., Alabaster, Ala.); STIMULON™ (QS-21); Quil-A (Quil-A saponin); S-28463 (4-amino-otec-dimethyl-2-ethoxymethyl-1H-imidazo[4,5-c]quinoline-1-ethanol); SAF-1™ (“Syntex adjuvant formulation”); Sendai proteoliposomes and Sendai-containing lipid matrices; Span-85 (sorbitan trioleate); Specol (emulsion of Marcol 52, Span 85 and Tween 85); squalene or Robane® (2,6,10,15,19,23-hexamethyltetracosan and 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexane); stearyltyrosine (octadecyltyrosine hydrochloride); Theramid® (N-acetylglucosaminyl-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-dipalmitoxypropylamide); Theronyl-MDP (Termurtide™ or [thr 1]-MDP; N-acetylmuramyl-L-threonyl-D-isoglutamine); Ty particles (Ty-VLPs or virus-like particles); Walter-Reed liposomes (liposomes containing lipid A adsorbed on aluminium hydroxide), and lipopeptides, including Pam3Cys, in particular aluminium salts, such as Adju-phos, Alhydrogel, Rehydragel, etc.; emulsions, such as CFA, SAF, IFA, MF59, Provax, TiterMax, Montanide, Vaxfectin, etc.; copolymers, such as Optivax (CRL1005), L121, Poloaxmer4010), etc.; liposomes, such as Stealth, etc., cochleates, such as BIORAL, etc.; plant derived adjuvants, such as QS21, Quil A, Iscomatrix, ISCOM, etc.; preferred adjuvants suitable for costimulation may include e.g. Tomatine, biopolymers, such as PLG, PMM, Inulin, etc.; microbe derived adjuvants, such as Romurtide, DETOX, MPL, CWS, Mannose, CpG7909, ISS-1018, IC31, Imidazoquinolines, Ampligen, Ribi529, IMOxine, IRIVs, VLPs, cholera toxin, heat-labile toxin, Pam3Cys, Flagellin, GPI anchor, LNFPIII/Lewis X, antimicrobial peptides, UC-1V150, RSV fusion protein, cdiGMP, etc.; preferred adjuvants suitable as antagonists may e.g. include CGRP neuropeptide,
or from cationic or polycationic compounds which are suitable for depot and delivery, including protamine, nucleoline, spermin or spermidine, or other cationic peptides or proteins, including poly-L-lysine (PLL), poly-arginine, basic polypeptides, cell penetrating peptides (CPPs), including HIV-binding peptides, Tat, HIV-1 Tat (HIV), Tat-derived peptides, Penetratin, VP22 derived or analog peptides, HSV VP22 (Herpes simplex), MAP, KALA or protein transduction domains (PTDs, PpT620, prolin-rich peptides, arginine-rich peptides, lysine-rich peptides, MPG-peptide(s), Pep-1, L-oligomers, Calcitonin peptide(s), Antennapedia-derived peptides (particularly from Drosophila antennapedia ), pAntp, plsl, FGF, Lactoferrin, Transportan, Buforin-2, Bac715-24, SynB, SynB(1), pVEC, hCT-derived peptides, SAP, protamine, spermine, spermidine, or histones. Additionally, preferred cationic or polycationic proteins or peptides may be selected from following proteins or peptides having the following total formula: (Arg) l ;(Lys) m ;(His) n ;(Orn) o ;(Xaa) x , wherein l+m+n+o+x=8-15, and l, m, n or o independently of each other may be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the overall content of Arg, Lys, His and Orn represents at least 50% of all amino acids of the oligopeptide; and Xaa may be any amino acid selected from native (=naturally occurring) or non-native amino acids except of Arg, Lys, His or Orn; and x may be any number selected from 0, 1, 2, 3 or 4, provided, that the overall content of Xaa does not exceed 50% of all amino acids of the oligopeptide, cationic polysaccharides, for example chitosan, polybrene, cationic polymers, including polyethyleneimine (PEI), cationic lipids, including DOTMA: [1-(2,3-sioleyloxy)propyl)]-N,N,N-trimethylammonium chloride, DMRIE, di-C14-amidine, DOTIM, SAINT, DC-Chol, BGTC, CTAP, DOPC, DODAP, DOPE: Dioleyl phosphatidylethanol-amine, DOSPA, DODAB, DOIC, DMEPC, DOGS: Dioctadecylamidoglicylspermin, DIMRI: Dimyristo-oxypropyl dimethyl hydroxyethyl ammonium bromide, DOTAP: dioleoyloxy-3-(trimethylammonio)propane, DC-6-14: O,O-ditetradecanoyl-N-(α-trimethylammonioacetyl)diethanolamine chloride, CLIP1: rac-[(2,3-dioctadecyloxypropyl)(2-hydroxyethyl)]-dimethylammonium chloride, CLIP6: rac-[2(2,3-dihexadecyloxypropyl-oxymethyloxy)ethyl]trimethylammonium, CLIPS: rac-[2(2,3-dihexadecyloxypropyl-oxysuccinyloxy)ethyl]-trimethylammonium, oligofectamine, or cationic or polycationic polymers, including modified polyaminoacids, including β-aminoacid-polymers or reversed polyamides, modified polyethylenes, including PVP (poly(N-ethyl-4-vinylpyridinium bromide)) modified acrylates, including pDMAEMA (poly(dimethylaminoethyl methylacrylate)), modified Amidoamines including pAMAM (poly(amidoamine)), modified polybetaaminoester (PBAE), including diamine end modified 1,4 butanediol diacrylate-co-5-amino-1-pentanol polymers dendrimers, including polypropylamine dendrimers or pAMAM based dendrimers, polyimine(s), including PEI: poly(ethyleneimine), poly(propyleneimine), polyallylamine, sugar backbone based polymers, including cyclodextrin based polymers, dextran based polymers, Chitosan, silan backbone based polymers, including PMOXA-PDMS copolymers, blockpolymers consisting of a combination of one or more cationic blocks (including selected og a cationic polymer as mentioned above) and of one or more hydrophilic- or hydrophobic blocks (e.g polyethyleneglycole);
or may be selected from nucleic acids of formula (IV): G l X m G n , wherein: G is guanosine, uridine or an analogue of guanosine or uridine; X is guanosine, uridine, adenosine, thymidine, cytidine or an analogue of the above-mentioned nucleotides; l is an integer from 1 to 40, wherein when l=1 G is guanosine or an analogue thereof, when l>1 at least 50% of the nucleotides are guanosine or an analogue thereof; m is an integer and is at least 3; wherein when m=3 X is uridine or an analogue thereof, when m>3 at least 3 successive uridines or analogues of uridine occur; n is an integer from 1 to 40, wherein when n=1 G is guanosine or an analogue thereof, when n>1 at least 50% of the nucleotides are guanosine or an analogue thereof;
or from nucleic acids of formula (V): C l X m C n , wherein: C is cytidine, uridine or an analogue of cytidine or uridine; X is guanosine, uridine, adenosine, thymidine, cytidine or an analogue of the above-mentioned nucleotides; l is an integer from 1 to 40, wherein when l=1 C is cytidine or an analogue thereof, when l>1 at least 50% of the nucleotides are cytidine or an analogue thereof; m is an integer and is at least 3; wherein when m=3 X is uridine or an analogue thereof, when m>3 at least 3 successive uridines or analogues of uridine occur; n is an integer from 1 to 40, wherein when n=1 C is cytidine or an analogue thereof, when n>1 at least 50% of the nucleotides are cytidine or an analogue thereof.
18 . Pharmaceutical composition according to claim 14 to 17 , characterized in that the pharmaceutical composition is a vaccine.
19 - 23 . (canceled)
24 . Kit containing a nucleic acid according to claim 1 , and also optionally technical instructions for use with information on the administration and dosage of the nucleic acid or the pharmaceutical composition.
25 . Method of treating a disorder or disease selected from the group consisting of cancer disease, infectious disease, autoimmune disease and allergy by administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid according to claim 1 .Join the waitlist — get patent alerts
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