BR112012026471A2 - conjugado, processo para a síntese do mesmo, método para imagem de uma célula que expressa um transportador de neurotransmissor que compreende o contato da referida célula com o conjugado, processo para preparar um comporto de fórmula (ii) e (xiv) e composto - Google Patents
conjugado, processo para a síntese do mesmo, método para imagem de uma célula que expressa um transportador de neurotransmissor que compreende o contato da referida célula com o conjugado, processo para preparar um comporto de fórmula (ii) e (xiv) e compostoInfo
- Publication number
- BR112012026471A2 BR112012026471A2 BR112012026471A BR112012026471A BR112012026471A2 BR 112012026471 A2 BR112012026471 A2 BR 112012026471A2 BR 112012026471 A BR112012026471 A BR 112012026471A BR 112012026471 A BR112012026471 A BR 112012026471A BR 112012026471 A2 BR112012026471 A2 BR 112012026471A2
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- Prior art keywords
- conjugate
- cell
- nucleic acid
- imaging
- xiv
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- 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
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32551510P | 2010-04-19 | 2010-04-19 | |
| EP10382087A EP2380595A1 (en) | 2010-04-19 | 2010-04-19 | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
| EP11382031 | 2011-02-09 | ||
| PCT/EP2011/056270 WO2011131693A2 (en) | 2010-04-19 | 2011-04-19 | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112012026471A2 true BR112012026471A2 (pt) | 2016-11-29 |
Family
ID=44063382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112012026471A BR112012026471A2 (pt) | 2010-04-19 | 2011-04-19 | conjugado, processo para a síntese do mesmo, método para imagem de uma célula que expressa um transportador de neurotransmissor que compreende o contato da referida célula com o conjugado, processo para preparar um comporto de fórmula (ii) e (xiv) e composto |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US9193969B2 (https=) |
| EP (2) | EP3231446B1 (https=) |
| JP (1) | JP5819401B2 (https=) |
| KR (1) | KR20130103662A (https=) |
| AR (1) | AR083715A1 (https=) |
| AU (4) | AU2011244321A1 (https=) |
| BR (1) | BR112012026471A2 (https=) |
| CA (1) | CA2796722C (https=) |
| DK (1) | DK2560687T3 (https=) |
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Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057179A2 (en) | 2002-01-11 | 2003-07-17 | Biomarin Pharmaceutical, Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| CA2796722C (en) | 2010-04-19 | 2021-06-01 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
| CA2817960C (en) | 2010-11-17 | 2020-06-09 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| CN103747807B (zh) | 2011-07-05 | 2016-12-07 | 比奥阿赛斯技术有限公司 | P97‑抗体缀合物和使用方法 |
| CN107115352B (zh) | 2011-08-04 | 2020-10-30 | 耶达研究及发展有限公司 | 微rna和包含微rna的组合物 |
| WO2013086207A1 (en) * | 2011-12-06 | 2013-06-13 | The Ohio State University | Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease |
| EP2831232A4 (en) | 2012-03-30 | 2015-11-04 | Univ Washington | METHOD FOR MODULATING TAU EXPRESSION TO REDUCE PROBLEMS AND MODIFY A NEURODEGENERATIVE SYNDROME |
| CA3140358A1 (en) | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| AU2013336582A1 (en) * | 2012-10-26 | 2015-06-11 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to cell types |
| EP2911695B1 (en) * | 2012-10-26 | 2023-11-29 | Palomo Limited | Compositions and methods for the treatment of parkinson disease by the selective delivery of oligonucleotide molecules to specific neuron types |
| CN104837996A (zh) | 2012-11-15 | 2015-08-12 | 罗氏创新中心哥本哈根有限公司 | 抗apob反义缀合物化合物 |
| EP2743695A1 (en) | 2012-12-12 | 2014-06-18 | Nanogap Sub NM Powder, S.A. | Methods and reagents for the detection of biomolecules using luminescence |
| AU2014243816B2 (en) | 2013-03-13 | 2019-01-31 | Bioasis Technologies Inc. | Fragments of p97 and uses thereof |
| CN105264091B (zh) | 2013-03-14 | 2020-02-28 | Ionis制药公司 | 用于调节tau表达的组合物和方法 |
| CN104178515B (zh) * | 2013-05-21 | 2018-08-31 | 成都先导药物开发有限公司 | 一种化合物的细胞透膜的方法 |
| WO2014187315A1 (zh) * | 2013-05-21 | 2014-11-27 | 成都先导药物开发有限公司 | 一种化合物给药前体及药物载体制剂 |
| EP3000898B1 (en) * | 2013-05-21 | 2020-11-18 | Hitgen Inc. | Drug target capturing method |
| TW202246503A (zh) | 2013-07-19 | 2022-12-01 | 美商百健Ma公司 | 用於調節τ蛋白表現之組合物 |
| JP6603227B2 (ja) | 2014-02-03 | 2019-11-06 | バイオアシス テクノロジーズ インコーポレイテッド | P97融合タンパク質 |
| CA2936158C (en) | 2014-02-05 | 2023-06-13 | Yeda Research And Development Co. Ltd. | Use of mir-135 or precursor thereof for the treatment and diagnosis of a bipolar disease |
| DK3107562T3 (da) | 2014-02-19 | 2019-12-16 | Bioasis Technologies Inc | P97-ids-fusionsproteiner |
| AU2015252906C1 (en) * | 2014-05-01 | 2020-09-17 | Bioasis Technologies Inc. | p97-polynucleotide conjugates |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| AU2015327836B2 (en) | 2014-10-03 | 2021-07-01 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
| IL320434A (en) | 2015-07-22 | 2025-06-01 | Wave Life Sciences Ltd | Oligonucleotide preparations and methods |
| US10733023B1 (en) * | 2015-08-06 | 2020-08-04 | D2Iq, Inc. | Oversubscription scheduling |
| DK3133166T4 (da) * | 2015-08-21 | 2023-03-20 | 42 Life Sciences Gmbh & Co Kg | Sammensætning og fremgangsmåde til hybridisering |
| CN108603230A (zh) | 2015-10-09 | 2018-09-28 | 南安普敦大学 | 基因表达的调节与蛋白质表达失调的筛选 |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| WO2017106377A1 (en) | 2015-12-14 | 2017-06-22 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of autosomal dominant mental retardation-5 and dravet syndrome |
| GB2574525B (en) * | 2015-12-21 | 2020-09-02 | Sutura Therapeutics Ltd | Improved drug delivery by conjugating oligonucleotides to stitched/stapled peptides |
| GB2545898B (en) | 2015-12-21 | 2019-10-09 | Sutura Therapeutics Ltd | Improved drug delivery by conjugating oligonucleotides to stitched/stapled peptides |
| DK3473270T5 (da) * | 2016-06-20 | 2024-09-09 | Genahead Bio Inc | Konjugat af antistof-lægemiddel |
| KR101916652B1 (ko) * | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| US10208098B2 (en) * | 2016-09-15 | 2019-02-19 | Council Of Scientific & Industrial Research | Recombinant protein-based method for the delivery of silencer RNA to target the brain |
| HUE065170T2 (hu) | 2016-09-29 | 2024-05-28 | Biogen Ma Inc | Vegyületek és módszerek a TAU expresszió csökkentésére |
| KR102318434B1 (ko) | 2017-08-25 | 2021-11-01 | 스톡 테라퓨틱스, 인크. | 병태 및 질환 치료용 안티센스 올리고머 |
| US11642365B2 (en) | 2017-09-22 | 2023-05-09 | John Mansell | Compositions and methods for treatment of sepsis-related disorders |
| EP3461487A1 (en) * | 2017-09-29 | 2019-04-03 | Nlife Therapeutics S.L. | Compositions and methods for the delivery of mrna to hepatic cells |
| HUE070436T2 (hu) | 2017-10-23 | 2025-06-28 | Stoke Therapeutics Inc | Antiszensz oligomerek nonszensz-mediált RNS-lebomláson alapuló állapotok és betegségek kezelésére |
| CN111787942B (zh) | 2017-10-25 | 2024-03-29 | 杨森制药公司 | 磷酸化Tau肽的组合物及其用途 |
| TWI809004B (zh) | 2017-11-09 | 2023-07-21 | 美商Ionis製藥公司 | 用於降低snca表現之化合物及方法 |
| SG11202006142PA (en) | 2018-01-12 | 2020-07-29 | Roche Innovation Ct Copenhagen As | Alpha-synuclein antisense oligonucleotides and uses thereof |
| SG11202006528XA (en) | 2018-01-12 | 2020-08-28 | Bristol Myers Squibb Co | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| CN120310791A (zh) | 2018-01-12 | 2025-07-15 | 百时美施贵宝公司 | 靶向α-突触核蛋白的反义寡核苷酸及其用途 |
| CA3099280A1 (en) | 2018-05-04 | 2019-11-07 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| CN119264211A (zh) | 2018-08-27 | 2025-01-07 | 瑞泽恩制药公司 | 拉曼光谱在下游纯化中的应用 |
| ES2698565B2 (es) * | 2018-12-12 | 2019-07-16 | Univ Madrid Complutense | Procedimiento para la elaboración de nanopartículas lipídicas, y nanopartículas lipídicas con los macrófagos cerebrales como células diana |
| MY206596A (en) | 2019-02-08 | 2024-12-25 | Janssen Pharmaceuticals Inc | Method of safe administration of phosphorylated tau peptide vaccine |
| AU2020227825B2 (en) | 2019-02-27 | 2026-03-26 | Stoke Therapeutics, Inc. | Antisense oligomers for treatment of conditions and diseases |
| US12478684B2 (en) | 2019-04-11 | 2025-11-25 | Northeastern University | Oligonucleotide-polymer miktoarm conjugates and methods of use |
| EP3983077A4 (en) * | 2019-06-17 | 2023-12-20 | Alnylam Pharmaceuticals, Inc. | DELIVERY OF OLIGONUCLEOTIDES TO THE STRIATUM |
| CN115867657A (zh) | 2020-05-11 | 2023-03-28 | 斯托克制药公司 | 用于治疗疾患和疾病的opa1反义寡聚物 |
| JP2024503711A (ja) * | 2021-01-18 | 2024-01-26 | イェダ リサーチ アンド デベロップメント カンパニー リミテッド | 修飾miR-135、そのコンジュゲートおよびその使用 |
| WO2024069229A2 (en) | 2022-08-03 | 2024-04-04 | Sutura Therapeutics Ltd | Biologically active compounds |
| US12396981B2 (en) | 2023-03-09 | 2025-08-26 | William Shulman | Methods of using DMT |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003042162A1 (en) * | 2001-11-17 | 2003-05-22 | Neurosearch A/S | Prodrugs of antidepressants and their use for treating depressions |
| EP1336406A1 (en) * | 2002-02-14 | 2003-08-20 | Solvay Pharmaceuticals B.V. | Partial dopamine-D2 receptor agonist plus serotonin and/or noradrenaline inhibitory activity |
| JP2007525211A (ja) * | 2004-01-19 | 2007-09-06 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | パーキンソン病の診断検査 |
| WO2007050789A2 (en) * | 2005-10-25 | 2007-05-03 | Nëdken Corporation | Glycosyl-oligonucleotide conjugates and methods |
| GB0605337D0 (en) | 2006-03-17 | 2006-04-26 | Genomica Sau | Treatment of CNS conditions |
| WO2008033285A2 (en) * | 2006-09-15 | 2008-03-20 | The Trustees Of Culumbia University In The City Of New York | Delivery of double-stranded rna into the central nervous system |
| BRPI0821310A2 (pt) * | 2007-12-20 | 2015-06-16 | Angiochem Inc | Conjugados polipeptídeos-ácido nucleico e usos dos mesmos |
| GB0809476D0 (en) * | 2008-05-23 | 2008-07-02 | Cambridge Entpr Ltd | Treatment of neurodegenerative disorders |
| DE102009058769A1 (de) * | 2009-12-16 | 2011-06-22 | MagForce Nanotechnologies AG, 10589 | Temperaturabhängige Aktivierung von katalytischen Nukleinsäuren zur kontrollierten Wirkstofffreisetzung |
| CA2796722C (en) | 2010-04-19 | 2021-06-01 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
| CA2817960C (en) * | 2010-11-17 | 2020-06-09 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| AU2013336582A1 (en) | 2012-10-26 | 2015-06-11 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to cell types |
| EP2911695B1 (en) | 2012-10-26 | 2023-11-29 | Palomo Limited | Compositions and methods for the treatment of parkinson disease by the selective delivery of oligonucleotide molecules to specific neuron types |
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2015
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| MX2012012214A (es) | 2013-02-07 |
| CA2796722C (en) | 2021-06-01 |
| JP5819401B2 (ja) | 2015-11-24 |
| WO2011131693A3 (en) | 2012-02-16 |
| AU2020202533B2 (en) | 2022-01-20 |
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| US10071163B2 (en) | 2018-09-11 |
| AU2019203887B2 (en) | 2020-01-23 |
| ES2638309T3 (es) | 2017-10-19 |
| CN103025357A (zh) | 2013-04-03 |
| EP2560687B1 (en) | 2017-05-24 |
| KR20130103662A (ko) | 2013-09-24 |
| US20160235856A1 (en) | 2016-08-18 |
| AU2020202533A1 (en) | 2020-05-07 |
| RU2664452C2 (ru) | 2018-08-17 |
| AU2019203887A1 (en) | 2019-07-18 |
| EP3231446A1 (en) | 2017-10-18 |
| AU2017204529A1 (en) | 2017-07-20 |
| DK2560687T3 (en) | 2017-09-18 |
| US20120322991A1 (en) | 2012-12-20 |
| JP2013525330A (ja) | 2013-06-20 |
| EP3231446B1 (en) | 2026-01-07 |
| LT2560687T (lt) | 2017-09-25 |
| AR083715A1 (es) | 2013-03-20 |
| CA2796722A1 (en) | 2011-10-27 |
| MX342764B (es) | 2016-10-12 |
| AU2011244321A1 (en) | 2012-11-15 |
| RU2012149042A (ru) | 2014-05-27 |
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| B15K | Others concerning applications: alteration of classification |
Ipc: A61K 31/135 (2006.01), A61K 31/472 (2006.01), A61K |
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Owner name: NLIFE THERAPEUTICS, S.L. (ES) Free format text: INDEFERIDO(S) O(S) PEDIDO(S) DE TRANSFERENCIA(S) CONTIDO(S) NA PETICAO 870190137658 DE 20/12/2019 EM VIRTUDE DO DESPACHO PUBLICADO NA RPI NO 2421 DE 30/05/2017. |