HRP20221547T1 - Inhibicija tmprss6 posredovana interferencijom rna - Google Patents
Inhibicija tmprss6 posredovana interferencijom rna Download PDFInfo
- Publication number
- HRP20221547T1 HRP20221547T1 HRP20221547TT HRP20221547T HRP20221547T1 HR P20221547 T1 HRP20221547 T1 HR P20221547T1 HR P20221547T T HRP20221547T T HR P20221547TT HR P20221547 T HRP20221547 T HR P20221547T HR P20221547 T1 HRP20221547 T1 HR P20221547T1
- Authority
- HR
- Croatia
- Prior art keywords
- nucleic acid
- structural strand
- seq
- acid according
- conjugated
- Prior art date
Links
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 title 1
- 230000009368 gene silencing by RNA Effects 0.000 title 1
- 230000005764 inhibitory process Effects 0.000 title 1
- 230000001404 mediated effect Effects 0.000 title 1
- 108020004707 nucleic acids Proteins 0.000 claims 32
- 150000007523 nucleic acids Chemical class 0.000 claims 32
- 102000039446 nucleic acids Human genes 0.000 claims 32
- 125000003729 nucleotide group Chemical group 0.000 claims 13
- 239000002773 nucleotide Substances 0.000 claims 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- ZGYYPTJWJBEXBC-QYYRPYCUSA-N (2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1F ZGYYPTJWJBEXBC-QYYRPYCUSA-N 0.000 claims 2
- 208000019838 Blood disease Diseases 0.000 claims 2
- 208000007209 Erythropoietic Porphyria Diseases 0.000 claims 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 claims 2
- 208000018565 Hemochromatosis Diseases 0.000 claims 2
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 2
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 2
- 206010036182 Porphyria acute Diseases 0.000 claims 2
- 230000000295 complement effect Effects 0.000 claims 2
- 201000008230 cutaneous porphyria Diseases 0.000 claims 2
- 210000000267 erythroid cell Anatomy 0.000 claims 2
- 230000010437 erythropoiesis Effects 0.000 claims 2
- 208000014951 hematologic disease Diseases 0.000 claims 2
- 208000018706 hematopoietic system disease Diseases 0.000 claims 2
- 229910052742 iron Inorganic materials 0.000 claims 2
- 239000003446 ligand Substances 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 230000004048 modification Effects 0.000 claims 2
- 210000003924 normoblast Anatomy 0.000 claims 2
- 210000000952 spleen Anatomy 0.000 claims 2
- 208000018240 Bone Marrow Failure disease Diseases 0.000 claims 1
- 208000035220 Dyserythropoietic Congenital Anemia Diseases 0.000 claims 1
- 102000001554 Hemoglobins Human genes 0.000 claims 1
- 108010054147 Hemoglobins Proteins 0.000 claims 1
- 101000798696 Homo sapiens Transmembrane protease serine 6 Proteins 0.000 claims 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
- 201000010273 Porphyria Cutanea Tarda Diseases 0.000 claims 1
- 206010036186 Porphyria non-acute Diseases 0.000 claims 1
- 206010041660 Splenomegaly Diseases 0.000 claims 1
- 101150114298 TMPRSS6 gene Proteins 0.000 claims 1
- 102100032452 Transmembrane protease serine 6 Human genes 0.000 claims 1
- 208000007502 anemia Diseases 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 208000005980 beta thalassemia Diseases 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 201000004440 congenital dyserythropoietic anemia Diseases 0.000 claims 1
- 210000003743 erythrocyte Anatomy 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000035800 maturation Effects 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
- 208000007056 sickle cell anemia Diseases 0.000 claims 1
- 229940126836 transmembrane protease serine 6 synthesis reducer Drugs 0.000 claims 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
- C12N15/1137—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 enzymes
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
-
- 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 N.A.
-
- 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
- C12N2310/31—Chemical structure of the backbone
- C12N2310/312—Phosphonates
-
- 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
- C12N2310/31—Chemical structure of the backbone
- C12N2310/313—Phosphorodithioates
-
- 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
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/31—Chemical structure of the backbone
- C12N2310/317—Chemical structure of the backbone with an inverted bond, e.g. a cap structure
-
- 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
- C12N2310/321—2'-O-R Modification
-
- 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
- C12N2310/322—2'-R Modification
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
-
- 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
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- 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
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
-
- 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
- C12N2310/35—Nature of the modification
- C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
- C12N2310/3521—Methyl
-
- 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
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
- C12N2310/3533—Halogen
-
- 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
- C12N2310/50—Physical structure
- C12N2310/51—Physical structure in polymeric form, e.g. multimers, concatemers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (18)
1. Nukleinska kiselina za inhibiranje ekspresije TMPRSS6, naznačena time, da sadrži najmanje jednu dupleks regiju koja sadrži prvu strukturnu nit i drugu strukturnu nit koja je barem djelomično komplementarna prvoj strukturnoj niti, pri čemu je navedena prva strukturna nit barem djelomično komplementarna odsječku RNA koja je transkribirana iz TMPRSS6 gena, gdje navedena nukleinska kiselina sadrži sljedeću prvu strukturnu nit:
5' – 3': aaccagaagaagcagguga;
opcionalno gdje nukleinska kiselina nadalje sadrži sljedeću drugu strukturnu nit:
5' – 3': ucaccugcuucuucugguu.
2. Nukleinska kiselina prema patentnom zahtjevu 1, naznačena time, da su jedan ili više nukleotida na prvoj strukturnoj niti i/ili drugoj strukturnoj niti modificirani, kako bi formirali modificirane nukleotide.
3. Nukleinska kiselina prema patentnom zahtjevu 2, naznačena time, da navedena prva strukturna nit sadrži nukleotidni slijed SEQ ID NO: 17, i time, da navedena druga strukturna nit sadrži nukleotidni slijed SEQ ID NO: 18:
SEQ ID NO: 17 5'aaccagaagaagcagguga 3' 6273646282647284546
SEQ ID NO: 18 5'ucaccugcuucuucugguu 3' 1727354715351718451
pri čemu su specifične modifikacije predstavljene sa sljedećim brojevima
1=2'F-dU,
2=2'F-dA,
3=2'F-dC,
4=2'F-dG,
5=2'-OMe-rU;
6=2'-OMe-rA;
7=2'-OMe-rC;
8=2'-OMe-rG.
4. Nukleinska kiselina prema patentnom zahtjevu 1, naznačena time, da se prva strukturna nit sastoji od slijeda:
5' – 3': aaccagaagaagcagguga.
5. Nukleinska kiselina prema patentnom zahtjevu 4, naznačena time, da su jedan ili više nukleotida na prvoj strukturnoj niti i/ili drugoj strukturnoj niti modificirani, kako bi formirali modificirane nukleotide.
6. Nukleinska kiselina prema patentnom zahtjevu 5, naznačena time, da se navedena prva strukturna nit sastoji od nukleotidnog slijeda SEQ ID NO: 17, i time, da navedena druga strukturna nit sadrži nukleotidni slijed SEQ ID NO: 18:
SEQ ID NO: 17 5'aaccagaagaagcagguga 3' 6273646282647284546
SEQ ID NO: 18 5'ucaccugcuucuucugguu 3' 1727354715351718451
pri čemu su specifične modifikacije predstavljene sa sljedećim brojevima
1=2'F-dU,
2=2'F-dA,
3=2'F-dC,
4=2'F-dG,
5=2'-OMe-rU;
6=2'-OMe-rA;
7=2'-OMe-rC;
8=2'-OMe-rG.
7. Nukleinska kiselina prema bilo kojem od prethodnih patentnih zahtjeva, naznačena time, da je konjugirana na ligand, opcionalno na kraju 5' od druge strukturne niti.
8. Konjugirana nukleinska kiselina prema patentnom zahtjevu 7, naznačena time, da ligand sadrži (i) jedan ili više ostataka N-acetil galaktozamina (GalNAc) i njegovih derivata, i (ii) poveznik, pri čemu poveznik konjugira ostatke GalNAc na nukleinsku kiselinu.
9. Konjugirana nukleinska kiselina prema patentnom zahtjevu 7 ili zahtjevu 8, naznačena time, da poveznik je bivalentna ili trivalentna ili tetravalentna razgranata struktura.
10. Konjugirana nukleinska kiselina prema bilo kojem od patentnih zahtjeva 7 do 9, naznačena time, da posjeduje strukturu:
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
pri čemu Z je nukleinska kiselina u skladu s bilo kojim od patentnih zahtjeva 1 do 6.
11. Nukleinska kiselina prema bilo kojem od patentnih zahtjeva 1 do 6, ili konjugirana nukleinska kiselina prema bilo kojem od patentnih zahtjeva 7 do 10, naznačena time, da je nukleinska kiselina stabilizirana na kraju 5' i/ili na kraju 3' od bilo koje strukturne niti ili od obje.
12. Nukleinska kiselina ili konjugirana nukleinska kiselina prema patentnom zahtjevu 11, naznačena time, da sadrži fosforotioatni poveznik između terminalnih jednog, dva ili tri nukleotida 3' i/ili nukleotida 5' od prve i/ili druge strukturne niti, ili sadrži fosforoditioatni poveznik.
13. Nukleinska kiselina ili konjugirana nukleinska kiselina prema patentnom zahtjevu 12, naznačena time, da sadrži fosforotioatni poveznik između svakog od tri terminalna nukleotida 3' i između svakog od tri terminalna nukleotida 5' na prvoj strukturnoj niti, i fosforotioatni poveznik između tri terminalna nukleotida od kraja 3' druge strukturne niti, koja ima strukturu:
5' – 3' TMPRSS6-hcm-9A SEQ ID NO: 17 6 (ps) 2 (ps) 736462826472845 (ps) 4 (ps) 6
5' – 3' TMPRSS6-hcm-9B SEQ ID NO: 18 17273547153517184 (ps) 5 (ps) 1
14. Pripravak, naznačen time, da sadrži nukleinsku kiselinu ili konjugiranu nukleinsku kiselinu prema bilo kojem od prethodnih patentnih zahtjeva i fiziološki prihvatljivo pomoćno sredstvo.
15. Nukleinska kiselina ili konjugirana nukleinska kiselina ili pripravak prema bilo kojem od prethodnih patentnih zahtjeva, naznačeni time, da su za uporabu u liječenju.
16. Nukleinska kiselina ili konjugirana nukleinska kiselina ili pripravak prema bilo kojem od prethodnih patentnih zahtjeva, naznačeni time, da su za uporabu u liječenju bolesti ili poremećaja, pri čemu se bolest ili poremećaj bira iz skupine koju čine hemokromatoza, eritropoetska porfirija, porfirija cutanea tarda i poremećaji krvi, kao što su β-talasemija ili bolest srpastih stanica, kongenitalna diseritropoetska anemija, sindromi zatajenja koštane srži, mijelodisplazija i prekomjerno transfuzijsko željezo.
17. Nukleinska kiselina ili konjugirana nukleinska kiselina ili pripravak za uporabu prema patentnom zahtjevu 16, naznačeni time, da se navedena bolest ili poremećaj bira iz skupine koju čine hemokromatoza, eritropoetska porfirija, prekomjerno transfuzijsko željezo i poremećaji krvi.
18. Nukleinska kiselina ili konjugirana nukleinska kiselina za uporabu prema bilo kojem od patentnih zahtjeva 15 do 17, naznačeni time, da je nukleinska kiselina za jedno ili više od sljedećih ili za sve navedeno:
(i) liječenje anemije, opcionalno prikladno utvrđene preko povećanja hemoglobina; i/ili
(ii) popravljanje splenomegalije, opcionalno utvrđene preko smanjenja veličine slezene ili težine; i/ili
(iii) smanjivanje naglašene eritropoeze u slezeni, opcionalno utvrđene preko omjera eritroblasta i enukleiranih eritroidnih stanica utvrđenog FACS analizom; i/ili
(iv) pospješivanje sazrijevanja/eritropoeze crvenih krvnih stanica u koštanoj srži, opcionalno utvrđenih preko omjera eritroblasta i enukleiranih eritroidnih stanica utvrđenog FACS analizom.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP17165007.0A EP3385380A1 (en) | 2017-04-05 | 2017-04-05 | Products and compositions |
EP17201405 | 2017-11-13 | ||
EP18715705.2A EP3607068B1 (en) | 2017-04-05 | 2018-04-05 | Rna interference mediated inhibition of tmprss6 |
PCT/EP2018/058764 WO2018185240A1 (en) | 2017-04-05 | 2018-04-05 | Products and compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20221547T1 true HRP20221547T1 (hr) | 2023-03-03 |
Family
ID=61899310
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20221547TT HRP20221547T1 (hr) | 2017-04-05 | 2018-04-05 | Inhibicija tmprss6 posredovana interferencijom rna |
Country Status (18)
Country | Link |
---|---|
US (2) | US11174483B2 (hr) |
EP (2) | EP3607068B1 (hr) |
JP (4) | JP7247167B2 (hr) |
KR (1) | KR102589803B1 (hr) |
CN (2) | CN110573619A (hr) |
AU (2) | AU2018247924B2 (hr) |
CA (2) | CA3057561A1 (hr) |
DK (1) | DK3607068T3 (hr) |
ES (1) | ES2936109T3 (hr) |
FI (1) | FI3607068T3 (hr) |
HR (1) | HRP20221547T1 (hr) |
HU (1) | HUE061894T2 (hr) |
IL (2) | IL269576B1 (hr) |
LT (1) | LT3607068T (hr) |
PL (1) | PL3607068T3 (hr) |
RS (1) | RS63887B1 (hr) |
SI (1) | SI3607068T1 (hr) |
WO (1) | WO2018185240A1 (hr) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3057565A1 (en) * | 2017-04-05 | 2018-10-11 | Silence Therapeutics Gmbh | Products and compositions |
EP3607067A1 (en) | 2017-04-05 | 2020-02-12 | Silence Therapeutics GmbH | Products and compositions |
EP3598995A1 (en) * | 2018-07-26 | 2020-01-29 | Silence Therapeutics GmbH | Products and compositions |
CN111973619B (zh) * | 2019-05-23 | 2024-01-30 | 苏州瑞博生物技术股份有限公司 | 核酸、含有该核酸的药物组合物与siRNA缀合物及制备方法和用途 |
JP2024515800A (ja) | 2021-04-27 | 2024-04-10 | サイレンス・セラピューティクス・ゲーエムベーハー | 骨髄増殖性障害の処置のためのTMPRSS6を標的とするsiRNA |
TW202400193A (zh) | 2022-06-24 | 2024-01-01 | 丹麥商諾佛 儂迪克股份有限公司 | 抑制跨膜絲胺酸蛋白酶6(tmprss6)表現的組成物及方法 |
WO2024060649A1 (zh) * | 2022-09-29 | 2024-03-28 | 广州必贝特医药股份有限公司 | 用于抑制TMPRSS6基因表达的siRNA或其盐、药物及其应用 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL9201440A (nl) | 1992-08-11 | 1994-03-01 | Univ Leiden | Triantennaire clusterglycosiden, hun bereiding en toepassing. |
PT2284266E (pt) * | 2002-11-14 | 2013-12-17 | Thermo Fisher Scient Biosciences Inc | Siarn contra tp53 |
JP6005628B2 (ja) * | 2010-04-28 | 2016-10-12 | アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. | 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物 |
BR112013025006B1 (pt) * | 2011-03-29 | 2021-06-15 | Alnylam Pharmaceuticals, Inc | Composição farmacêutica para inibir a expressão de um gene de tmprss6, método para inibição da expressão de tmprss6 em uma célula, e uso de ácidos ribonu-cleicos fita dupla |
EP3650544A1 (en) * | 2011-11-07 | 2020-05-13 | Ionis Pharmaceuticals, Inc. | Modulation of tmprss6 expression |
TW202342750A (zh) * | 2013-05-22 | 2023-11-01 | 美商阿尼拉製藥公司 | TMPRSS6 iRNA組成物及其使用方法 |
KR102630289B1 (ko) * | 2014-08-20 | 2024-01-31 | 알닐람 파마슈티칼스 인코포레이티드 | 변형 이중-가닥 rna 제제 |
WO2016085852A1 (en) * | 2014-11-24 | 2016-06-02 | Alnylam Pharmaceuticals, Inc. | Tmprss6 irna compositions and methods of use thereof |
US20160272970A1 (en) * | 2015-03-17 | 2016-09-22 | Arrowhead Madison Inc. | RNA Interference Agents |
EP3228326A1 (en) | 2016-04-05 | 2017-10-11 | Silence Therapeutics GmbH | Nucleic acid linked to a trivalent glycoconjugate |
-
2018
- 2018-04-05 RS RS20230024A patent/RS63887B1/sr unknown
- 2018-04-05 JP JP2020504435A patent/JP7247167B2/ja active Active
- 2018-04-05 CA CA3057561A patent/CA3057561A1/en active Pending
- 2018-04-05 US US16/500,703 patent/US11174483B2/en active Active
- 2018-04-05 AU AU2018247924A patent/AU2018247924B2/en active Active
- 2018-04-05 CN CN201880021535.3A patent/CN110573619A/zh active Pending
- 2018-04-05 EP EP18715705.2A patent/EP3607068B1/en active Active
- 2018-04-05 HR HRP20221547TT patent/HRP20221547T1/hr unknown
- 2018-04-05 WO PCT/EP2018/058764 patent/WO2018185240A1/en unknown
- 2018-04-05 FI FIEP18715705.2T patent/FI3607068T3/fi active
- 2018-04-05 ES ES18715705T patent/ES2936109T3/es active Active
- 2018-04-05 IL IL269576A patent/IL269576B1/en unknown
- 2018-04-05 SI SI201830837T patent/SI3607068T1/sl unknown
- 2018-04-05 EP EP22202522.3A patent/EP4219714A3/en active Pending
- 2018-04-05 DK DK18715705.2T patent/DK3607068T3/da active
- 2018-04-05 PL PL18715705.2T patent/PL3607068T3/pl unknown
- 2018-04-05 HU HUE18715705A patent/HUE061894T2/hu unknown
- 2018-04-05 KR KR1020197032297A patent/KR102589803B1/ko active IP Right Grant
- 2018-04-05 LT LTEPPCT/EP2018/058764T patent/LT3607068T/lt unknown
-
2019
- 2019-04-05 CN CN201980037644.9A patent/CN112424354A/zh active Pending
- 2019-04-05 CA CA3095523A patent/CA3095523A1/en active Pending
- 2019-04-05 AU AU2019247637A patent/AU2019247637A1/en active Pending
- 2019-04-05 JP JP2020554254A patent/JP7419252B2/ja active Active
-
2020
- 2020-09-29 IL IL277636A patent/IL277636A/en unknown
-
2021
- 2021-10-05 US US17/450,064 patent/US20220025377A1/en active Pending
-
2023
- 2023-03-14 JP JP2023039774A patent/JP2023068035A/ja active Pending
-
2024
- 2024-01-09 JP JP2024001366A patent/JP2024036347A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20221547T1 (hr) | Inhibicija tmprss6 posredovana interferencijom rna | |
HRP20230127T1 (hr) | Nukleinske kiseline za inhibiranje ekspresije lpa u stanici | |
JP2018536689A5 (hr) | ||
JP2018519835A5 (hr) | ||
RU2016101198A (ru) | Доставка, применение и применения в терапии систем crispr-cas и композиций для целенаправленного воздействия на нарушения и заболевания с использованием вирусных компонентов | |
JP2016520593A5 (hr) | ||
HRP20211971T1 (hr) | Pripravci i postupci za inhibiciju ekspresije gena hao1 (hidroksikiselina oksidaza 1 (glikolat oksidaza)) | |
EA015570B1 (ru) | Фармацевтическая композиция | |
US9970007B2 (en) | Targeting microRNAs for the treatment of fibrosis | |
JP2015523853A5 (hr) | ||
WO2008109447B1 (en) | Nucleic acid compounds for inhibiting met gene expression and uses thereof | |
CN102712927A (zh) | 通过抑制膜结合转录因子肽酶,位点1(mbtps1)的天然反义转录物来治疗mbtps1相关疾病 | |
WO2008008719A3 (en) | Compositions and methods for inhibiting expression of the myc gene | |
WO2011066312A1 (en) | Minor groove binder (mgb)-oligonucleotide mirna antagonists | |
CN102482672A (zh) | 通过抑制唐氏综合征基因的天然反义转录物治疗唐氏综合征基因相关疾病 | |
CN102869777A (zh) | 通过抑制集落刺激因子3(csf3)的天然反义转录物而治疗csf3相关疾病 | |
JP2023068035A5 (hr) | ||
US20230295626A1 (en) | Targeted Inhibition Using Engineered Oligonucleotides | |
JP2020518552A5 (hr) | ||
EP3257515A1 (en) | Antitumor agent | |
US8729046B2 (en) | MIR27B is a novel target for treatment of liver fibrosis | |
HRP20211525T1 (hr) | Molekule sirna specifične za notch 1 | |
WO2008109350A3 (en) | Nucleic acid compounds for inhibiting il6 gene expression and uses thereof | |
WO2009152500A4 (en) | Methods and compositions for mediating gene silencing | |
WO2008109354B1 (en) | Nucleic acid compounds for inhibiting il18 gene expression and uses thereof |