WO2008109350A4 - Nucleic acid compounds for inhibiting il6 gene expression and uses thereof - Google Patents
Nucleic acid compounds for inhibiting il6 gene expression and uses thereof Download PDFInfo
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- WO2008109350A4 WO2008109350A4 PCT/US2008/055333 US2008055333W WO2008109350A4 WO 2008109350 A4 WO2008109350 A4 WO 2008109350A4 US 2008055333 W US2008055333 W US 2008055333W WO 2008109350 A4 WO2008109350 A4 WO 2008109350A4
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- 230000014509 gene expression Effects 0.000 title claims abstract 12
- 101150101999 IL6 gene Proteins 0.000 title claims abstract 5
- 108020004707 nucleic acids Proteins 0.000 title claims abstract 5
- 102000039446 nucleic acids Human genes 0.000 title claims abstract 5
- -1 Nucleic acid compounds Chemical class 0.000 title claims 3
- 230000002401 inhibitory effect Effects 0.000 title 1
- 230000000295 complement effect Effects 0.000 claims abstract 12
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 11
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims abstract 6
- 108020004999 messenger RNA Proteins 0.000 claims abstract 6
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims abstract 5
- 238000012986 modification Methods 0.000 claims abstract 5
- 230000004048 modification Effects 0.000 claims abstract 5
- 102000004889 Interleukin-6 Human genes 0.000 claims abstract 4
- 108090001005 Interleukin-6 Proteins 0.000 claims abstract 4
- 239000002777 nucleoside Substances 0.000 claims abstract 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract 3
- 229920002477 rna polymer Polymers 0.000 claims abstract 3
- 239000002773 nucleotide Substances 0.000 claims 26
- 125000003729 nucleotide group Chemical group 0.000 claims 26
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 7
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 6
- YHRRPHCORALGKQ-FDDDBJFASA-N 2'-O-methyl-5-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C)=C1 YHRRPHCORALGKQ-FDDDBJFASA-N 0.000 claims 5
- SNNBPMAXGYBMHM-JXOAFFINSA-N 5-methyl-2-thiouridine Chemical compound S=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SNNBPMAXGYBMHM-JXOAFFINSA-N 0.000 claims 5
- 102000052611 human IL6 Human genes 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 101100286713 Homo sapiens IL6 gene Proteins 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 229910019142 PO4 Inorganic materials 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 3
- 239000010452 phosphate Substances 0.000 claims 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 238000000137 annealing Methods 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 210000005260 human cell Anatomy 0.000 claims 2
- 229940116886 human interleukin-6 Drugs 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 230000003463 hyperproliferative effect Effects 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 229940100601 interleukin-6 Drugs 0.000 claims 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 239000002718 pyrimidine nucleoside Substances 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 101100282111 Caenorhabditis elegans gap-2 gene Proteins 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 2
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000030279 gene silencing Effects 0.000 abstract 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 abstract 1
- 229940045145 uridine Drugs 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing IL6 gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to an IL6 mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine, a nucleoside replaced with a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of an IL6 gene in a cell or in a subject to treat an IL6-related disease.
Claims
1. A meroduplex ribonucleic acid (mdRNA) molecule that down regulates the expression of a human interleukin 6 (IL6) mRNA, the mdRNA molecule comprising a first strand of 15 to 40 nucleotides in length that is complementary to a portion of a nucleic acid sequence as set forth in SEQ ID NO: 1158 or 1159, and a second strand and a third strand that is each complementary to non-overlapping regions of the first strand, wherein the second strand and third strand can anneal with the first strand to form at least two double-stranded regions spaced apart by a nick or a gap-
2. The mdRNA molecule of claim 1 wherein the first strand is 15 to 25 nucleotides in length or 26 to 40 nucleotides in length.
3. The mdRNA molecule of claim 1 wherein the gap comprises from 1 to 10 unpaired nucleotides.
4. The mdRNA molecule of claim 1 wherein the mdRNA molecule comprises at least one 5-methyluridine, 2-thioribothymidine, or 2'-O-methyl-5- methyluridine.
5. The mdRNA molecule of claim 1 wherein the mdRNA molecule comprises at least one locked nucleic acid (LNA) molecule, deoxy nucleotide, G clamp, 2'-sugar modification, modified internucleoside linkage, or any combination thereof.
6. The mdRNA molecule of claim 1 wherein the mdRNA contains an overhang of one to four nucleotides on at least one 3 '-end that is not part of the gap or has a blunt end at one or both ends of the mdRNA.
7. An mdRNA molecule that down regulates the expression of a human IL6 mRNA, the mdRNA molecule comprising a first strand of 15 to 40 nucleotides in length that is complementary to a portion of a nucleic acid sequence as set forth in SEQ ID NO: 1158 or 1159, and a second strand and a third strand that is each complementary to non-overlapping regions of the first strand, wherein the second strand and third strand can anneal with the first strand to form at least two double-stranded regions spaced apart by a nick or a gap, and wherein at least one
83 pyrimidine of the mdRNA molecule is a pyrimidine nucleoside according to Formula I or II:
wherein:
R1 and R2 are each independently a -H, -OH, -OCH3, -OCH2OCH2CH3, -OCH2CH2OCH3, halogen, substituted or unsubstituted Ci-Ci0 alkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkylsulfonylamino, aminoalkyl, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, haloalkyl, trifluoromethyl, cycloalkyl, (cycloalkyl)alkyl, substituted or unsubstituted C2-Ci0 alkenyl, substituted or unsubstituted -O-allyl, -0-CH2CH=CH2, -0-CH=CHCH3, substituted or unsubstituted C2-Ci0 alkynyl, carbamoyl, carbamyl, carboxy, carbonylamino, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, -NH2, -NO2, -C≡, or heterocyclo group,
R3 and R4 are each independently a hydroxyl, a protected hydroxyl, a phosphate, or an internucleoside linking group, and
R5 and R8 are each independently O or S.
8. The mdRNA molecule of claim 7 wherein the first strand is 15 to 25 nucleotides in length or 26 to 40 nucleotides in length.
9. The mdRNA molecule of claim 7 wherein the gap comprises from 1 to 10 unpaired nucleotides.
10. The mdRNA molecule of claim 7 wherein at least one nucleoside is according to Formula I and in which R1 is methyl and R2 is -OH or -O-methyl.
84
11. The mdRNA molecule of claim 7 wherein at least one R2 is selected from the group consisting of 2'-0-(Ci-C5) alkyl, 2'-O-methyl, 2'-OCH2OCH2CH3,
2' -OCH2CH2OCH3, 2'-0-allyl, and fluoro.
12. The mdRNA molecule of claim 7 wherein the mdRNA molecule comprises at least one 5-methyluridine, 2-thioribothymidine, or 2'-O-methyl-5- methyluridine.
13. The mdRNA molecule of claim 7 wherein the mdRNA molecule comprises at least one locked nucleic acid (LNA) molecule, deoxy nucleotide, G clamp, 2'-sugar modification, modified internucleoside linkage, or any combination thereof.
14. The mdRNA molecule of claim 7 wherein contains an overhang of one to four nucleotides on at least one 3 '-end that is not a part of the gap or the dsRNA molecule has a blunt end on one or both ends of the mdRNA molecule.
15. An mdRNA molecule that down regulates the expression of a human IL6 mRNA, the mdRNA molecule comprising a first strand of 15 to 40 nucleotides in length that is complementary to a portion of a nucleic acid sequence as set forth in SEQ ID NO: 1158 or 1159, and a second strand and a third strand that is each complementary to non-overlapping regions of the first strand, wherein the second strand and third strand can anneal with the first strand to form at least two double- stranded regions spaced apart by a nick or a gap, and wherein the double-stranded regions have a combined length of about 15 base pairs to about 40 base pairs.
16. The mdRNA molecule of claim 15 wherein the first strand is 15 to 25 nucleotides in length or 26 to 40 nucleotides in length.
17. The mdRNA molecule of claim 15 wherein the gap comprises from 1 to 10 unpaired nucleotides.
18. The mdRNA molecule of claim 15 wherein the mdRNA molecule comprises at least one 5-methyluridine, 2-thioribothymidine, or 2'-O-methyl-5- methyluridine.
85
19. The mdRNA molecule of claim 15 wherein the first strand is 19 to 23 nucleotides in length and is complementary to a human IL6 nucleic acid sequence as set forth in any one of SEQ ID NOS: 158, 1160-1381.
20. The mdRNA molecule of claim 15 wherein the first strand is 25 to 29 nucleotides in length and is complementary to a human IL6 nucleic acid sequence as set forth in any one of SEQ ID NOS:158, 1160-1381.
21. A method for reducing the expression of a human IL6 gene, comprising administering an mdRNA molecule according to any one of claims 1-20 to a cell expressing the human IL6 gene, wherein the mdRNA molecule reduces the expression of the human IL6 gene in the cell.
22. The method according to claim 21 wherein the cell is a human cell.
23. Use of an mdRNA as defined in any one of the preceding claims for the manufacture of a medicament for use in the therapy of a hyperproliferative or inflammatory disease.
24. A double-stranded ribonucleic acid (dsRNA) molecule that down regulates the expression of a human interleukin 6 (IL6) mRNA, the dsRNA molecule comprising a first strand of 26 to 40 nucleotides in length that is complementary to a portion of a nucleic acid sequence as set forth in any one of SEQ ID NO: 1158 or
1 159, and a second strand that is complementary to the first strand, and wherein upon annealing of the first strand and the second strand the dsRNA has a 3' overhang and a blunt end.
25. The dsRNA molecule of claim 24 wherein the first strand is from 27 to 35 nucleotides in length.
26. The dsRNA molecule of claim 24 wherein the dsRNA molecule comprises at least one 5-methyluridine, 2-thioribothymidine, or 2'-O-methyl-5- methyluridine.
27. The dsRNA molecule of claim 24 wherein the dsRNA molecule comprises at least one locked nucleic acid (LNA) molecule, deoxy nucleotide, G
86 clamp, 2'-sugar modification, modified intemucleoside linkage, or any combination thereof.
28. The dsRNA molecule of claim 24 wherein the 3'-overhang has from one to four nucleotides and is on the first strand.
29. The dsRNA molecule of claim 24 wherein the dsRNA molecule has a 5'-terminal end comprising a hydroxyl or a phosphate.
30. A dsRNA molecule that down regulates the expression of a human IL6 mRNA, the dsRNA molecule comprising a first strand of 26 to 40 nucleotides in length that is complementary to a portion of a nucleic acid sequence as set forth in any one of SEQ ID NO:1 158 or 1159, and wherein upon annealing of the first strand and the second strand the dsRNA has a 3' overhang and a blunt end, and wherein at least one pyrimidine of the dsRNA molecule comprises a pyrimidine nucleoside according to Formula I or II:
R1 and Rz are each independently a -H, -OH, -OCH3, -OCH2OCH2CH3, -OCH2CH2OCH3, halogen, substituted or unsubstituted C]-C]0 alkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkylsulfonylamino, aminoalkyl, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, haloalkyl, trifluoromethyl, cycloalkyl, (cycloalkyl)alkyl, substituted or unsubstituted C2-C]0 alkenyl, substituted or unsubstituted -O-allyl, -0-CH2CH=CH2, -0-CH=CHCH3, substituted or unsubstituted C2-C]0 alkynyl, carbamoyl, carbamyl, carboxy, carbonylamino, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, -NH2, -NO2, -C≡N, or heterocyclo group,
R and R4 are each independently a hydroxyl, a protected hydroxyl, a phosphate, or an intemucleoside linking group, and
87 R5 and R8 are each independently O or S.
31. The dsRNA molecule of claim 30 wherein the first strand is from 27 to 35 nucleotides in length.
32. The dsRNA molecule of claim 30 wherein at least one nucleoside is according to Formula I and in which R1 is methyl and R2 is -OH or -O-methyl.
33. The dsRNA molecule of claim 30 wherein at least one R2 is selected from the group consisting of 2'-0-(C1-C5) alkyl, 2'-O-methyl, 2'-OCH2OCH2CH3, 2'-OCH2CH2OCH3, 2'-O-allyl, and 2'-fluoro.
34. The dsRNA molecule of claim 30 wherein the dsRNA molecule comprises at least one 5-methyluridine, 2-thioribothymidine, or 2'-O-methyl-5- methyluridine.
35. The dsRNA molecule of claim 30 wherein the dsRNA molecule comprises at least one LNA, deoxy nucleotide, G clamp, 2'-sugar modification, modified internucleoside linkage, or any combination thereof.
36. The dsRNA molecule of claim 30, wherein the 3'-overhang has from one to four nucleotides and is on the first strand.
37. A method for reducing the expression of a human IL6 gene, comprising administering a dsRNA molecule according to any one of claims 24-36 to a cell expressing the IL6 gene, wherein the dsRNA molecule reduces the expression of the IL6 gene in the cell.
38. The method according to claim 37 wherein the cell is a human cell.
39. Use of a dsRNA molecule as defined in any one of claims 24-38 for the manufacture of a medicament for use in the therapy of a hyperproliferative or inflammatory disease.
88
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2009212920A AU2009212920A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| US12/552,082 US20100105134A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| US13/327,545 US20130011922A1 (en) | 2007-03-02 | 2011-12-15 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93494007P | 2007-03-02 | 2007-03-02 | |
| US60/934,940 | 2007-03-02 | ||
| US93493007P | 2007-03-16 | 2007-03-16 | |
| US60/934,930 | 2007-03-16 | ||
| US97079607P | 2007-09-07 | 2007-09-07 | |
| US60/970,796 | 2007-09-07 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055341 Continuation-In-Part WO2008109354A1 (en) | 2007-03-02 | 2008-02-28 | Nucleic acid compounds for inhibiting il18 gene expression and uses thereof |
Related Child Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055382 Continuation-In-Part WO2008109379A1 (en) | 2007-03-02 | 2008-02-28 | Nucleic acid compounds for inhibiting il17a gene expression and uses thereof |
| US12/552,082 Continuation-In-Part US20100105134A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| AU2009212920A Division AU2009212920A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO2008109350A2 WO2008109350A2 (en) | 2008-09-12 |
| WO2008109350A9 WO2008109350A9 (en) | 2008-12-11 |
| WO2008109350A3 WO2008109350A3 (en) | 2009-02-19 |
| WO2008109350A4 true WO2008109350A4 (en) | 2009-04-23 |
Family
ID=39739026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055333 WO2008109350A2 (en) | 2007-03-02 | 2008-02-28 | Nucleic acid compounds for inhibiting il6 gene expression and uses thereof |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2009212920A1 (en) |
| WO (1) | WO2008109350A2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9074205B2 (en) | 2006-10-18 | 2015-07-07 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
| JP5475643B2 (en) * | 2007-05-04 | 2014-04-16 | マリーナ バイオテック，インコーポレイテッド | Amino acid lipids and uses thereof |
| WO2010028054A1 (en) | 2008-09-02 | 2010-03-11 | Alnylam Europe Ag. | Compositions and methods for inhibiting expression of mutant egfr gene |
| CN106636090B (en) * | 2016-10-11 | 2019-08-09 | 上海优卡迪生物医药科技有限公司 | siRNA of human interleukin 6, recombinant expression CAR-T vector and its construction method and application |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080066987A (en) * | 2005-11-04 | 2008-07-17 | 나스텍 파마수티컬 컴퍼니 인코포레이티드 | Peptide-Dicer Substrates RNA Conjugates as Delivery Carriers for SiRNA |
| EP2002004B1 (en) * | 2006-03-23 | 2015-10-14 | Roche Innovation Center Copenhagen A/S | Small internally segmented interfering rna |
| US9074205B2 (en) * | 2006-10-18 | 2015-07-07 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
-
2008
- 2008-02-28 WO PCT/US2008/055333 patent/WO2008109350A2/en active Application Filing
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2009
- 2009-09-01 AU AU2009212920A patent/AU2009212920A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008109350A3 (en) | 2009-02-19 |
| WO2008109350A9 (en) | 2008-12-11 |
| AU2009212920A8 (en) | 2009-10-22 |
| AU2009212920A1 (en) | 2009-10-01 |
| WO2008109350A2 (en) | 2008-09-12 |
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