Patent application EP17153389A (EP), filed 2009-04-22
Publication number: EP3248618A1
Title: INNATE IMMUNE SUPPRESSION ENABLES REPEATED DELIVERY OF LONG RNA MOLECULES
Abstract: [0001]    Disclosed are methods for suppressing the innate immune response of a cell to transfection with an exogenous nucleic acid. Further disclosed are methods for increasing expression of a protein encoded by an exogenous nucleic acid by repeated delivery of the exogenous nucleic acid to a cell, and methods of changing the phenotype of a cell by differentiating, transdifferentiating or dedifferentiating cells by repeatedly delivering one or more nucleic acids that encode defined proteins. A method is provided for extended transient transfection by repeated delivery of an in vitro-transcribed RNA ("ivT-RNA) to a cell to achieve a high and sustained level of expression of a protein encoded by an ivT-RNA transcripts.
IPC codes: A61K  39/   395            A I
A61K  48/    00            A I
C07H  21/    02            A I
Claims: number: 1
text: An agent that inhibits IFNK1 in the innate immune response pathway for use in a method of suppressing the innate immune response of an animal administered with a nucleic acid molecule,
wherein the animal is exposed to the agent before or simultaneously with administration of said nucleic acid molecule,
the agent optionally being used in combination with one or more siRNA or antisense agents targeting expression of a protein in the innate immune response pathway selected from the group consisting of TP53, TLR3, TLR7, RARRES3, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21, IFNK, IFNB1, IL6, TICAM1, TICAM2, MAVS, STAT1, STAT2, EIF2AK2, IRF3, TBK1, CDKN1A, CDKN2A, RNASEL, IFNAR1, IFNAR2, OAS1, OAS2, OAS3, OASL, RB1, ISG15, ISG20, IFIT1, IFIT2, IFIT3, and IFIT5; and
wherein the agent is B18R.
number: 2
text: The agent of claim 1, wherein the animal is a human.
number: 3
text: The agent of claim 1 or claim 2, wherein the one or more siRNA or antisense agents are specifically hybridizable to an RNA or DNA molecule encoding IFNB1, STAT2, TP53 and/or EIF2AK2.
number: 4
text: The agent of any one of claims 1-3, wherein the nucleic acid molecule administered to the animal encodes a protein, biologically active fragment thereof or an RNA molecule.
number: 5
text: The agent of claim 5, wherein the protein affects or controls cellular phenotype.
number: 6
text: The agent of any one of claims 1-5, wherein the exposure to the agent and the administration of the nucleic acid molecule are simultaneous; or wherein the exposure to an agent is repeated two or more times; or wherein the administration of the nucleic acid molecule is repeated two or more times; or wherein the exposure to the agent is performed up to about 24-72 hours before the administration of the nucleic acid molecule.
number: 7
text: The agent of any one of claims 1-6, wherein the nucleic acid molecule is RNA.
number: 8
text: The agent of any one of claims 1-6, wherein the nucleic acid molecule is an oligonucleotide.
number: 9
text: The agent of claim 8 wherein the oligonucleotide comprises a modified nucleobase.
number: 10
text: The agent of claim 9, wherein the modified nucleobase is selected from 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (-C=C-CH3) uracil and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8- substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-aminoadenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine.
number: 11
text: The agent of any one of claims 1-10, wherein the siRNA is 20 to 29 nucleotides.
number: 12
text: The agent of any one of claims 1-11, wherein the nucleic acid molecule comprises a 2'-O-methyl modification.
number: 13
text: The agent of any one of claims 1-12, wherein the nucleic acid molecule is a plasmid, a vector, or an RNA transcript.
Office action: search_report, dated 2017-11-29
Rejection reasons: novelty_epc_54
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Final disposition: pending (2017-11-29)