JP2020530981A5 - - Google Patents
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- JP2020530981A5 JP2020530981A5 JP2019572710A JP2019572710A JP2020530981A5 JP 2020530981 A5 JP2020530981 A5 JP 2020530981A5 JP 2019572710 A JP2019572710 A JP 2019572710A JP 2019572710 A JP2019572710 A JP 2019572710A JP 2020530981 A5 JP2020530981 A5 JP 2020530981A5
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- JP
- Japan
- Prior art keywords
- antisense oligonucleotide
- exon
- cell
- target region
- optionally
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 108091034117 Oligonucleotide Proteins 0.000 claims description 83
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 69
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 69
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 21
- 108090000623 proteins and genes Proteins 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 150000007523 nucleic acids Chemical class 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 108020004414 DNA Proteins 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 229920002477 rna polymer Polymers 0.000 claims description 10
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 230000004957 immunoregulator effect Effects 0.000 claims description 8
- 108091033319 polynucleotide Proteins 0.000 claims description 8
- 102000040430 polynucleotide Human genes 0.000 claims description 8
- 239000002157 polynucleotide Substances 0.000 claims description 8
- 108700042075 T-Cell Receptor Genes Proteins 0.000 claims description 7
- -1 2- Methoxyethyl phosphodiester Chemical class 0.000 claims description 6
- 229940059260 amidate Drugs 0.000 claims description 6
- 108700024394 Exon Proteins 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 238000004520 electroporation Methods 0.000 claims description 5
- 108020004999 messenger RNA Proteins 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 102000001398 Granzyme Human genes 0.000 claims description 4
- 108060005986 Granzyme Proteins 0.000 claims description 4
- 102100037850 Interferon gamma Human genes 0.000 claims description 4
- 108010074328 Interferon-gamma Proteins 0.000 claims description 4
- 102000004503 Perforin Human genes 0.000 claims description 4
- 108010056995 Perforin Proteins 0.000 claims description 4
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 238000012986 modification Methods 0.000 claims description 4
- 230000004048 modification Effects 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 3
- 102100035990 Adenosine receptor A2a Human genes 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 3
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 3
- 101000783751 Homo sapiens Adenosine receptor A2a Proteins 0.000 claims description 3
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 3
- 102000017578 LAG3 Human genes 0.000 claims description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
- 108010029485 Protein Isoforms Proteins 0.000 claims description 3
- 102000001708 Protein Isoforms Human genes 0.000 claims description 3
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 3
- 230000000840 anti-viral effect Effects 0.000 claims description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- 235000011010 calcium phosphates Nutrition 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
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- 239000002773 nucleotide Substances 0.000 claims description 3
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 102000053602 DNA Human genes 0.000 claims description 2
- 239000004677 Nylon Substances 0.000 claims description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 claims description 2
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 claims description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 239000000412 dendrimer Substances 0.000 claims description 2
- 229920000736 dendritic polymer Polymers 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 238000002372 labelling Methods 0.000 claims description 2
- 229920001778 nylon Polymers 0.000 claims description 2
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 229930192851 perforin Natural products 0.000 claims description 2
- 150000004713 phosphodiesters Chemical group 0.000 claims description 2
- 150000008298 phosphoramidates Chemical class 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 230000009385 viral infection Effects 0.000 claims 2
- 238000000137 annealing Methods 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 claims 1
- 238000011394 anticancer treatment Methods 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
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- 230000035755 proliferation Effects 0.000 claims 1
- 239000002502 liposome Substances 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 239000002105 nanoparticle Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 108091026823 U7 small nuclear RNA Proteins 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229940126546 immune checkpoint molecule Drugs 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 102100024263 CD160 antigen Human genes 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 101150091887 Ctla4 gene Proteins 0.000 description 1
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 1
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 1
- 101000973157 Homo sapiens NEDD4 family-interacting protein 1 Proteins 0.000 description 1
- 101000884270 Homo sapiens Natural killer cell receptor 2B4 Proteins 0.000 description 1
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 1
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 102100022547 NEDD4 family-interacting protein 1 Human genes 0.000 description 1
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 description 1
- 102100024894 PR domain zinc finger protein 1 Human genes 0.000 description 1
- 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SG10201705285SA SG10201705285SA (en) | 2017-06-27 | 2017-06-27 | Antisense oligonucleotides |
| SG10201705285S | 2017-06-27 | ||
| PCT/SG2018/050313 WO2019004939A1 (en) | 2017-06-27 | 2018-06-27 | ANTISENSE OLIGONUCLEOTIDES FOR MODULATING THE FUNCTION OF A LYMPHOCYTE T |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020530981A JP2020530981A (ja) | 2020-11-05 |
| JP2020530981A5 true JP2020530981A5 (enExample) | 2021-07-29 |
| JP7284718B2 JP7284718B2 (ja) | 2023-05-31 |
Family
ID=64742433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019572710A Active JP7284718B2 (ja) | 2017-06-27 | 2018-06-27 | Ｔ細胞の機能を調節するためのアンチセンスオリゴヌクレオチド |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US12188016B2 (enExample) |
| EP (1) | EP3645724A4 (enExample) |
| JP (1) | JP7284718B2 (enExample) |
| KR (1) | KR20200035937A (enExample) |
| CN (1) | CN111630167B (enExample) |
| AU (1) | AU2018291556B2 (enExample) |
| CA (1) | CA3066035A1 (enExample) |
| SG (2) | SG10201705285SA (enExample) |
| WO (1) | WO2019004939A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3436572A4 (en) * | 2016-03-31 | 2019-11-20 | Lion TCR Pte. Ltd. | EXOGENOUS VIRUS-SPECIFIC T-CELL RECEPTOR (TCR) EXPRESSIVE UNACTIVATED T-CELLS |
| WO2017220751A1 (en) | 2016-06-22 | 2017-12-28 | Proqr Therapeutics Ii B.V. | Single-stranded rna-editing oligonucleotides |
| ES2837076T3 (es) | 2016-09-01 | 2021-06-29 | Proqr Therapeutics Ii Bv | Oligonucleótidos para la edición de ARN de cadena sencilla modificados químicamente |
| GB201808146D0 (en) | 2018-05-18 | 2018-07-11 | Proqr Therapeutics Ii Bv | Stereospecific Linkages in RNA Editing Oligonucleotides |
| US11312963B2 (en) * | 2018-10-18 | 2022-04-26 | Synerk Inc. | Compositions and methods for inhibiting TIGIT gene expression |
| CA3132178A1 (en) * | 2019-04-02 | 2020-10-08 | Aliye Seda Yilmaz-Elis | Antisense oligonucleotides for immunotherapy |
| CN109988842B (zh) * | 2019-04-19 | 2022-12-06 | 上海吉玛制药技术有限公司 | 一种寡核苷酸标记探针原位检测pdl1的试剂组与应用 |
| WO2020219977A1 (en) * | 2019-04-26 | 2020-10-29 | Stoke Therapeutics, Inc. | Methods and compositions for modulating splicing of alternative introns |
| CN110157705B (zh) * | 2019-05-16 | 2021-06-18 | 苏州安天圣施医药科技有限公司 | 在pdcd1基因表达的剪接水平抑制pd-1信号的反义寡核苷酸及其筛选方法与应用 |
| EP3974531A4 (en) * | 2019-05-20 | 2024-01-10 | Olix Pharmaceuticals, Inc. | Asymmetric sirna inhibiting expression of pd-1 |
| JP7337373B2 (ja) * | 2019-07-29 | 2023-09-04 | サイアス株式会社 | 抗原特異的ｔ細胞の製造方法 |
| WO2021127261A1 (en) * | 2019-12-17 | 2021-06-24 | The General Hospital Corporation | Engineered immune cells with reduced toxicity and uses thereof |
| WO2021173812A1 (en) * | 2020-02-28 | 2021-09-02 | Aligos Therapeutics, Inc. | Methods and compositions for targeting pd-l1 |
| AU2021266145A1 (en) * | 2020-04-30 | 2022-11-10 | Secarna Pharmaceuticals Gmbh & Co. Kg | PD-1-specific antisense oligonucleotide and its use in therapy |
| EP4211241A1 (en) * | 2020-09-10 | 2023-07-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of splice switching oligonucleotides for exon skipping-mediated knockdown of nf-kb components in b cells |
| WO2022084389A1 (en) * | 2020-10-20 | 2022-04-28 | Immunoa Pte. Ltd. | Modified immune cells |
| JP2024501662A (ja) | 2020-12-22 | 2024-01-15 | エフ． ホフマン－ラ ロシュ アーゲー | Ｘｂｐ１を標的とするオリゴヌクレオチド |
| EP4074835A1 (en) * | 2021-04-15 | 2022-10-19 | Deutsches Krebsforschungszentrum - Stiftung des öffentlichen Rechts / Universität Heidelberg | H-1 pv expressing rnai effectors |
| CN115216474B (zh) * | 2021-04-15 | 2025-09-30 | 武汉大学 | 促进pd-l1外显子3跳跃的反义寡核苷酸及其应用 |
| WO2023073709A1 (en) * | 2021-10-27 | 2023-05-04 | Hadasit Medical Research Services & Development Ltd. | Nucleic acid agents modulating pd-1 isoforms |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6566132B1 (en) * | 2001-04-26 | 2003-05-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of Interferon gamma receptor 1 expression |
| US8501704B2 (en) * | 2005-11-08 | 2013-08-06 | Sarepta Therapeutics, Inc. | Immunosuppression compound and treatment method |
| WO2007056466A2 (en) | 2005-11-08 | 2007-05-18 | Avi Biopharma, Inc. | Immunosuppression compound and treatment method |
| ES2645410T3 (es) * | 2006-05-10 | 2017-12-05 | Sarepta Therapeutics, Inc. | Análogos de oligonucleótidos que tienen enlaces intersubunitarios catiónicos |
| EP2295543A1 (en) * | 2009-09-11 | 2011-03-16 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Method for the preparation of an influenza virus |
| WO2011120101A1 (en) | 2010-04-01 | 2011-10-06 | The University Of Queensland | Small rna molecules and methods of use |
| EP2825665B1 (en) | 2012-03-14 | 2017-09-06 | Ruprecht-Karls-Universität Heidelberg | Epigenetic signatures as marker for cardiomyopathies and myocardial insufficiencies |
| US20150017136A1 (en) | 2013-07-15 | 2015-01-15 | Cellectis | Methods for engineering allogeneic and highly active t cell for immunotherapy |
| US9909128B2 (en) | 2012-11-15 | 2018-03-06 | The Regents Of The University Of California | Splice modulating oligonucleotides that inhibit cancer |
| WO2014090985A1 (en) * | 2012-12-13 | 2014-06-19 | Universität Leipzig | T-cell modulation by exon skipping |
| CN103820454B (zh) * | 2014-03-04 | 2016-03-30 | 上海金卫生物技术有限公司 | CRISPR-Cas9特异性敲除人PD1基因的方法以及用于特异性靶向PD1基因的sgRNA |
| WO2015161276A2 (en) * | 2014-04-18 | 2015-10-22 | Editas Medicine, Inc. | Crispr-cas-related methods, compositions and components for cancer immunotherapy |
| US9828601B2 (en) * | 2015-02-27 | 2017-11-28 | Idera Pharmaceuticals, Inc. | Compositions for inhibiting checkpoint gene expression and uses thereof |
| BR112017020750A2 (pt) | 2015-03-27 | 2018-06-26 | Harvard College | células t modificadas e métodos de produção e utilização das mesmas |
| WO2016196388A1 (en) * | 2015-05-29 | 2016-12-08 | Juno Therapeutics, Inc. | Composition and methods for regulating inhibitory interactions in genetically engineered cells |
| JP2018536436A (ja) | 2015-12-04 | 2018-12-13 | ノバルティス アーゲー | 免疫腫瘍学のための組成物および方法 |
-
2017
- 2017-06-27 SG SG10201705285SA patent/SG10201705285SA/en unknown
-
2018
- 2018-06-27 CA CA3066035A patent/CA3066035A1/en not_active Abandoned
- 2018-06-27 SG SG11201911704UA patent/SG11201911704UA/en unknown
- 2018-06-27 CN CN201880043866.7A patent/CN111630167B/zh active Active
- 2018-06-27 EP EP18823314.2A patent/EP3645724A4/en active Pending
- 2018-06-27 US US16/626,395 patent/US12188016B2/en active Active
- 2018-06-27 AU AU2018291556A patent/AU2018291556B2/en not_active Expired - Fee Related
- 2018-06-27 KR KR1020207000349A patent/KR20200035937A/ko not_active Withdrawn
- 2018-06-27 JP JP2019572710A patent/JP7284718B2/ja active Active
- 2018-06-27 WO PCT/SG2018/050313 patent/WO2019004939A1/en not_active Ceased
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