HRP20240672T1 - Pripravci i postupci za smanjenje tau ekspresije - Google Patents
Pripravci i postupci za smanjenje tau ekspresije Download PDFInfo
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- HRP20240672T1 HRP20240672T1 HRP20240672TT HRP20240672T HRP20240672T1 HR P20240672 T1 HRP20240672 T1 HR P20240672T1 HR P20240672T T HRP20240672T T HR P20240672TT HR P20240672 T HRP20240672 T HR P20240672T HR P20240672 T1 HRP20240672 T1 HR P20240672T1
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- 230000003247 decreasing effect Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 title 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 23
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 7
- 206010012289 Dementia Diseases 0.000 claims 4
- 238000012986 modification Methods 0.000 claims 4
- 208000017004 dementia pugilistica Diseases 0.000 claims 3
- 239000002773 nucleotide Substances 0.000 claims 3
- 125000003729 nucleotide group Chemical group 0.000 claims 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims 2
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 claims 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims 2
- 208000010577 Niemann-Pick disease type C Diseases 0.000 claims 2
- 208000027089 Parkinsonian disease Diseases 0.000 claims 2
- 206010034010 Parkinsonism Diseases 0.000 claims 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 2
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 claims 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 1
- 206010059245 Angiopathy Diseases 0.000 claims 1
- 208000014644 Brain disease Diseases 0.000 claims 1
- 208000009093 Diffuse Neurofibrillary Tangles with Calcification Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 201000007547 Dravet syndrome Diseases 0.000 claims 1
- 208000032274 Encephalopathy Diseases 0.000 claims 1
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 claims 1
- 201000004066 Ganglioglioma Diseases 0.000 claims 1
- 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 claims 1
- 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 claims 1
- 206010018341 Gliosis Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims 1
- 208000001089 Multiple system atrophy Diseases 0.000 claims 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims 1
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 1
- 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 claims 1
- 208000036757 Postencephalitic parkinsonism Diseases 0.000 claims 1
- 102000029797 Prion Human genes 0.000 claims 1
- 108091000054 Prion Proteins 0.000 claims 1
- 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 claims 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 claims 1
- 201000004810 Vascular dementia Diseases 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 208000013968 amyotrophic lateral sclerosis-parkinsonism-dementia complex Diseases 0.000 claims 1
- 208000014450 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 Diseases 0.000 claims 1
- 210000000349 chromosome Anatomy 0.000 claims 1
- 229940104302 cytosine Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010015037 epilepsy Diseases 0.000 claims 1
- 201000005649 gangliocytoma Diseases 0.000 claims 1
- 201000008361 ganglioneuroma Diseases 0.000 claims 1
- 230000007387 gliosis Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 201000008319 inclusion body myositis Diseases 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 208000005264 motor neuron disease Diseases 0.000 claims 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 claims 1
- 208000002593 pantothenate kinase-associated neurodegeneration Diseases 0.000 claims 1
- 150000004713 phosphodiesters Chemical class 0.000 claims 1
- 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 230000002739 subcortical effect Effects 0.000 claims 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 1
- 208000009999 tuberous sclerosis Diseases 0.000 claims 1
Classifications
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- 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
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/16—Anti-Parkinson drugs
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
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- C12N2310/321—2'-O-R Modification
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- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
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- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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Claims (15)
1. Oligonukleotid, naznačen time, što sadrži slijed nukleobaze koja ima najmanje 90% identičnosti slijeda sa:
GGTTGACATC GTCTGCCTGT (SEQ ID NO: 208 ili SEQ ID NO: 285),
pri čemu je C u bilo kojem od sljedova nukleobaze ili citozin ili 5-metilcitozin, i pri čemu najmanje jedan nukleotid od oligonukleotida ima 2'-modifikaciju.
2. Oligonukleotid prema patentnom zahtjevu 1, naznačen time, što oligonukleotid sadrži slijed nukleobaze koji ima najmanje 95% identičnosti slijeda sa:
GGTTGACATC GTCTGCCTGT (SEQ ID NO: 208 ili SEQ ID NO: 285).
3. Oligonukleotid prema patentnom zahtjevu 2, naznačen time, što oligonukleotid sadrži slijed nukleobaze:
GGTTGACATC GTCTGCCTGT (SEQ ID NO: 208 ili SEQ ID NO: 285).
4. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-3, naznačen time, što je internukleozidna veza oligonukleotida ili fosfodiesterska ili fosforotioatna veza.
5. Oligonukleotid prema patentnom zahtjevu 4, naznačen time, što je internukleozidna veza oligonukleotida fosforotioatna veza.
6. Oligonukleotid prema bilo kojem od patentnih zahtjeva 4-5, naznačen time, što oligonukleotid sadrži najmanje pet susjednih 2'-deoksinukleozida, poželjno najmanje sedam susjednih 2'-deoksinukleozida, poželjnije deset susjednih 2'-deoksinukleozida.
7. Oligonukleotid prema bilo kojem od patentnih zahtjeva 5-6, naznačen time, što oligonukleotid smanjuje tau mRNA ili ekspresiju proteina aktiviranjem RNAze H.
8. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-7, naznačen time, što svaki C u bilo kojem od sljedova nukleobaze jest 5-metilcitozin.
9. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-8, naznačen time, što je 2'-modifikacija odabrana iz skupine koju čine 2'-fluoro, 2'-deoksi-2'-fluoro, 2'-O-metil, 2'-O-mehoksietil (2'-O-MOE), 2'-O-aminopropil (2'-O-AP), 2'-O-dimetilaminoetil (2'-O-DMAOE), 2'-O-dimetilaminopropil (2'-O-DMAP), 2'-O-dimetilaminoetiloksietil (2'-O-DMAEOE), i 2'-O-N-metilacetamido (2'-O-NMA).
10. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-9, naznačen time, što je 2'-modifikacija 2'-O-metoksietil (2'-O-MOE).
11. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-10, naznačen time, što je oligonukleotid sposoban smanjiti razinu ekspresije tau mRNA ili proteina za najmanje 30% in vitro, ili za najmanje 30% in vivo.
12. Oligonukleotid, naznačen time, što sadrži slijed nukleobaze odabran iz skupine koju čine G*G*T*T*G*ACATCGTCTGC*C*T*G*T* (SEQ ID NO: 208) i G*G*T*T*G*AmCATmCGTmCTGmC*mC*T*G*T* (SEQ ID NO: 285) pri čemu nukleotidi sa * imaju 2'-O-MOE modifikaciju; nukleotidi bez * su 2'-deoksinukleozidi; mC predstavlja 5'-metilcitozin, a internukleozidne veze su fosforotioatne.
13. Pripravak, naznačen time, što sadrži oligonukleotid prema bilo kojem od patentnih zahtjeva 1-12 i farmaceutski prihvatljiv nosač.
14. Oligonukleotid prema bilo kojem od patentnih zahtjeva 1-12 ili pripravak prema patentnom zahtjevu 13, naznačen time, što je za uporabu u liječenju bolesti povezane s tau kod pojedinca kojemu je to potrebno.
15. Oligonukleotid za uporabu prema patentnom zahtjevu 14, naznačen time, što je bolest koja je povezana s tau odabrana iz skupine od Alzheimerove bolesti (AD), amiotrofične lateralne skleroze/kompleksa parkinsonizma i demencije (ALS-PDC), argirofilne zrnaste demencije (AGD), amiloidne angiopatije britanskog tipa, cerebralne amiloidne angiopatije, kronične traumatske encefalopatije (CTE), kortikobazalne degeneracije (CBD), Creutzfeldt-Jakobove bolesti (CJD), dementia pugilistica, difuznih neurofibrilarnih čvorova s kalcifikacijom, Downovog sindroma, Dravetovog sindroma, epilepsije, frontotemporalne demencije (FTD), frontotemporalne demencije s parkinsonizmom povezanim s kromosomom 17 (FTDP-17), frontotemporalne lobarne degeneracije, ganglioglioma, gangliocitoma, Gerstmann-Straussler-Scheinkerove bolesti, Hallervorden-Spatzove bolesti, Huntingtonove bolesti, miozitisa inkluzijskih tjelešaca, olovne encefalopatije, Lytico-Bodigove bolesti, meningioangiomatoze, multiple sistemske atrofije, miotonične distrofije, Niemann-Pickove bolesti tipa C (NP-C), ne-Guamanove bolesti motoričkih neurona s neurofibrilarnim čvorovima, Pickove bolesti (PiD), postencefalitičkog parkinsonizma, cerebralne amiloidne angiopatije prionskih proteina, progresivne subkortikalne glioze, progresivne supranuklearne paralize (PSP), subakutnog sklerozirajućeg panencefalitisa, demencije samo s petljama, demencije s prevladavajućim petljama, multi-infarktne demencije, ishemijskog moždanog udara, ili tuberozne skleroze.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562270165P | 2015-12-21 | 2015-12-21 | |
| PCT/IB2016/057794 WO2017109679A1 (en) | 2015-12-21 | 2016-12-19 | Compositions and methods for decreasing tau expression |
| EP16823350.0A EP3394259B1 (en) | 2015-12-21 | 2016-12-19 | Compositions and methods for decreasing tau expression |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20240672T1 true HRP20240672T1 (hr) | 2024-08-16 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20240672TT HRP20240672T1 (hr) | 2015-12-21 | 2016-12-19 | Pripravci i postupci za smanjenje tau ekspresije |
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| Country | Link |
|---|---|
| US (2) | US11473083B2 (hr) |
| EP (2) | EP3394259B1 (hr) |
| JP (4) | JP7027328B2 (hr) |
| CN (2) | CN109072237B (hr) |
| AR (1) | AR107579A1 (hr) |
| AU (2) | AU2016376034B2 (hr) |
| CA (1) | CA3008094A1 (hr) |
| CL (3) | CL2018001652A1 (hr) |
| CO (1) | CO2018006297A2 (hr) |
| CR (1) | CR20200609A (hr) |
| CU (1) | CU24574B1 (hr) |
| DK (1) | DK3394259T3 (hr) |
| DO (1) | DOP2018000151A (hr) |
| EA (2) | EA202091865A1 (hr) |
| EC (1) | ECSP18050575A (hr) |
| ES (1) | ES2984631T3 (hr) |
| FI (1) | FI3394259T3 (hr) |
| HR (1) | HRP20240672T1 (hr) |
| HU (1) | HUE066548T2 (hr) |
| IL (3) | IL296844B2 (hr) |
| JO (2) | JOP20200228A1 (hr) |
| LT (1) | LT3394259T (hr) |
| MA (2) | MA44426B1 (hr) |
| MX (2) | MX2018007726A (hr) |
| MY (1) | MY191737A (hr) |
| PE (2) | PE20241069A1 (hr) |
| PH (1) | PH12018501207B1 (hr) |
| PL (1) | PL3394259T3 (hr) |
| PT (1) | PT3394259T (hr) |
| RS (1) | RS65535B1 (hr) |
| RU (1) | RU2747734C2 (hr) |
| SA (1) | SA518391831B1 (hr) |
| SG (2) | SG11201804704PA (hr) |
| SI (1) | SI3394259T1 (hr) |
| SV (1) | SV2018005714A (hr) |
| TW (2) | TWI787163B (hr) |
| UY (1) | UY37038A (hr) |
| WO (1) | WO2017109679A1 (hr) |
| ZA (1) | ZA201803661B (hr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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