ES2971506T3 - Haptenos de paliperidona - Google Patents
Haptenos de paliperidona Download PDFInfo
- Publication number
- ES2971506T3 ES2971506T3 ES19177909T ES19177909T ES2971506T3 ES 2971506 T3 ES2971506 T3 ES 2971506T3 ES 19177909 T ES19177909 T ES 19177909T ES 19177909 T ES19177909 T ES 19177909T ES 2971506 T3 ES2971506 T3 ES 2971506T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- protein
- paliperidone
- compound
- hapten
- 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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- PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 title abstract description 44
- 229960001057 paliperidone Drugs 0.000 title abstract description 43
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 57
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 56
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- 230000015572 biosynthetic process Effects 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 125000006850 spacer group Chemical group 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 38
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- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 4
- FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 description 4
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
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- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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Landscapes
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- Zoology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
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| US201261691459P | 2012-08-21 | 2012-08-21 |
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| EP (2) | EP2888258B1 (https=) |
| JP (2) | JP6286429B2 (https=) |
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| AU (2) | AU2013305930B2 (https=) |
| CA (1) | CA2882555C (https=) |
| ES (2) | ES2971506T3 (https=) |
| PL (1) | PL2888258T3 (https=) |
| PT (1) | PT2888258T (https=) |
| TR (1) | TR201911272T4 (https=) |
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| JP6389177B2 (ja) | 2012-08-21 | 2018-09-12 | ヤンセン ファーマシューティカ エヌ．ベー． | オランザピンハプテンに対する抗体及びその使用 |
| ES2788716T3 (es) | 2012-08-21 | 2020-10-22 | Janssen Pharmaceutica Nv | Anticuerpos para haptenos de quetiapina y uso de los mismos |
| CN104736565B (zh) | 2012-08-21 | 2019-03-12 | 詹森药业有限公司 | 利培酮半抗原的抗体及其用途 |
| AU2013305930B2 (en) * | 2012-08-21 | 2017-08-24 | Saladax Biomedical Inc. | Haptens of paliperidone |
| EP3462173B1 (en) | 2012-08-21 | 2021-03-31 | Janssen Pharmaceutica NV | Antibodies to risperidone and use thereof |
| ES2654413T3 (es) | 2012-08-21 | 2018-02-13 | Janssen Pharmaceutica, N.V. | Anticuerpos a quetiapina y uso de los mismos |
| US9494608B2 (en) | 2012-08-21 | 2016-11-15 | Janssen Pharmaceutica Nv | Antibodies to olanzapine and use thereof |
| ES2978909T3 (es) | 2012-08-21 | 2024-09-23 | Janssen Pharmaceutica Nv | Anticuerpos contra haptenos de aripiprazol y uso de los mismos |
| ES2652641T3 (es) | 2012-08-21 | 2018-02-05 | Janssen Pharmaceutica Nv | Haptenos de aripiprazol y su uso en inmunoensayos |
| CA2882562C (en) | 2012-08-21 | 2019-08-27 | Eric Hryhorenko | Antibodies to aripiprazole and use thereof |
| CA2882490A1 (en) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc. | Antibodies to paliperidone and use thereof |
| JP2015529199A (ja) | 2012-08-21 | 2015-10-05 | オルソ−クリニカル ダイアグノスティクス，インコーポレイティド | パリペリドンハプテンに対する抗体及びその使用 |
| CN108431040B (zh) | 2015-12-17 | 2022-07-26 | 詹森药业有限公司 | 利培酮的抗体及其用途 |
| EP3390455A1 (en) | 2015-12-17 | 2018-10-24 | Janssen Pharmaceutica NV | Antibodies to quetiapine and use thereof |
| CN111751535B (zh) * | 2020-07-02 | 2023-07-11 | 北京勤邦科技股份有限公司 | 一种检测硫丹的试纸条及其应用 |
| CN116710144A (zh) * | 2020-12-22 | 2023-09-05 | 英特维特国际股份有限公司 | 防止真菌毒素中毒症的偶联的玉米赤霉烯酮 |
| CN116003404B (zh) * | 2022-12-14 | 2024-10-01 | 杭州同舟生物技术有限公司 | 一种利培酮人工半抗原、人工抗原及其制备方法和应用 |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
| US5284948A (en) * | 1991-06-07 | 1994-02-08 | Eastman Kodak Company | Drug hapten analogues for immunoassays |
| US6034078A (en) | 1992-05-29 | 2000-03-07 | Eli Lilly And Company Limited | Thienobenzodiazepine compounds |
| DK0582368T3 (da) | 1992-05-29 | 2001-02-05 | Lilly Co Eli | Thienobenzodiazepinderivater til behandling af forstyrrelser i centralnervesystemet |
| US5395933A (en) | 1992-08-07 | 1995-03-07 | Eastman Kodak Company | Carbamazepine hapten analogues |
| US6958156B2 (en) | 2000-12-15 | 2005-10-25 | Vyrex Corporation | Isoflavone derivatives |
| US7193065B2 (en) * | 2001-07-13 | 2007-03-20 | Roche Diagnostics Operations, Inc. | Protease inhibitor conjugates and antibodies useful in immunoassay |
| DE60335428D1 (de) * | 2002-01-31 | 2011-02-03 | Randox Lab Ltd | Immunogene, Antikörper und Konjugate für Ketamin und dessen Metaboliten |
| AU2003217936A1 (en) | 2002-03-28 | 2003-10-13 | Eli Lilly And Company | Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders |
| AU2003264915A1 (en) | 2002-08-05 | 2004-02-25 | Eli Lilly And Company | Piperazine substituted aryl benzodiazepines |
| ES2335589T3 (es) | 2003-09-23 | 2010-03-30 | Fermion Oy | Preparacion de quetiapina. |
| TW200616604A (en) | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| FR2878850B1 (fr) * | 2004-12-02 | 2008-10-31 | Cis Bio Internat Sa | Derives de l'inositol-1-phosphate |
| RU2010116351A (ru) | 2007-09-27 | 2012-05-20 | Новартис АГ (CH) | Мониторинг лекарственных средств |
| US20100069356A1 (en) | 2008-09-17 | 2010-03-18 | Auspex Pharmaceuticals, Inc. | Dibenzothiazepine modulators of dopamine, alpha adrenergic, and serotonin receptors |
| CN102245605B (zh) | 2008-10-14 | 2016-01-27 | 阿斯利康(瑞典)有限公司 | 用于治疗细菌感染的稠合、螺环杂芳族化合物 |
| EP2194048A1 (en) | 2008-12-02 | 2010-06-09 | Dirk Sartor | Nitrate esters for the treatment of vascular and metabolic diseases |
| CN102573913B (zh) * | 2009-07-31 | 2014-06-18 | 阿森迪斯药物股份有限公司 | 可生物降解的基于聚乙二醇的水不溶性水凝胶 |
| US20130053405A1 (en) * | 2009-10-06 | 2013-02-28 | Ulrich Hersel | Carrier linked paliperidone prodrugs |
| EP2343296A1 (en) * | 2009-12-01 | 2011-07-13 | Chemo Ibérica, S.A. | A process for the purification of paliperidone |
| CN107714703A (zh) | 2009-12-31 | 2018-02-23 | 凯姆制药公司 | 喹硫平的氨基酸缀合物、其制备和使用方法 |
| EP3476218A1 (en) | 2010-03-11 | 2019-05-01 | Kempharm, Inc. | Fatty acid conjugates of quetiapine, process for making and using the same |
| US8088594B2 (en) | 2010-03-16 | 2012-01-03 | Saladax Biomedical Inc. | Risperidone immunoassay |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| US8623324B2 (en) | 2010-07-21 | 2014-01-07 | Aat Bioquest Inc. | Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates |
| JP5757497B2 (ja) * | 2010-10-06 | 2015-07-29 | 公立大学法人大阪府立大学 | シガトキシン類ｃｔｘ１ｂおよび５４−デオキシ−ｃｔｘ１ｂを認識するモノクローナル抗体およびそれを用いるシガトキシン類検出キット |
| AU2012296950B2 (en) * | 2011-08-12 | 2016-09-22 | Ascendis Pharma A/S | Polymeric hyperbranched carrier-linked prodrugs |
| WO2013024047A1 (en) * | 2011-08-12 | 2013-02-21 | Ascendis Pharma A/S | High-loading water-soluble carrier-linked prodrugs |
| NZ722096A (en) | 2011-12-15 | 2016-11-25 | Alkermes Pharma Ireland Ltd | Prodrugs of secondary amine compounds |
| AU2013305930B2 (en) * | 2012-08-21 | 2017-08-24 | Saladax Biomedical Inc. | Haptens of paliperidone |
| EP3462173B1 (en) | 2012-08-21 | 2021-03-31 | Janssen Pharmaceutica NV | Antibodies to risperidone and use thereof |
| CN104736565B (zh) | 2012-08-21 | 2019-03-12 | 詹森药业有限公司 | 利培酮半抗原的抗体及其用途 |
| ES2654413T3 (es) | 2012-08-21 | 2018-02-13 | Janssen Pharmaceutica, N.V. | Anticuerpos a quetiapina y uso de los mismos |
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| CN104837838A (zh) | 2015-08-12 |
| US9394354B2 (en) | 2016-07-19 |
| JP2018095655A (ja) | 2018-06-21 |
| CN110003201A (zh) | 2019-07-12 |
| AU2017264978A1 (en) | 2017-12-07 |
| AU2017264978B2 (en) | 2019-09-12 |
| AU2013305930A1 (en) | 2015-03-05 |
| US20140213767A1 (en) | 2014-07-31 |
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