ES2701062T3 - Haptenos de olanzapina - Google Patents
Haptenos de olanzapina Download PDFInfo
- Publication number
- ES2701062T3 ES2701062T3 ES13753774T ES13753774T ES2701062T3 ES 2701062 T3 ES2701062 T3 ES 2701062T3 ES 13753774 T ES13753774 T ES 13753774T ES 13753774 T ES13753774 T ES 13753774T ES 2701062 T3 ES2701062 T3 ES 2701062T3
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- Prior art keywords
- methyl
- group
- compound
- hapten
- reaction
- Prior art date
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- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 title description 30
- 229960005017 olanzapine Drugs 0.000 title description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
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- 230000002163 immunogen Effects 0.000 claims description 53
- 108090000623 proteins and genes Proteins 0.000 claims description 33
- 102000004169 proteins and genes Human genes 0.000 claims description 32
- 230000008569 process Effects 0.000 claims description 26
- 229940092253 ovalbumin Drugs 0.000 claims description 11
- 101000800130 Bos taurus Thyroglobulin Proteins 0.000 claims description 10
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 claims description 10
- 108010058846 Ovalbumin Proteins 0.000 claims description 8
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 abstract 2
- -1 secondary amine compounds Chemical class 0.000 description 53
- 125000006850 spacer group Chemical group 0.000 description 50
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- 239000000243 solution Substances 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- 229940079593 drug Drugs 0.000 description 29
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—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
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—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
- 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
-
- A—HUMAN NECESSITIES
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/76—Albumins
- C07K14/77—Ovalbumin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261691454P | 2012-08-21 | 2012-08-21 | |
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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 |
| 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 |
| CA2882562C (en) | 2012-08-21 | 2019-08-27 | Eric Hryhorenko | Antibodies to aripiprazole 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 |
| ES2652641T3 (es) | 2012-08-21 | 2018-02-05 | Janssen Pharmaceutica Nv | Haptenos de aripiprazol y su uso en inmunoensayos |
| TR201816378T4 (tr) * | 2012-08-21 | 2018-11-21 | Janssen Pharmaceutica Nv | Olanzapin haptenleri. |
| ES2788716T3 (es) | 2012-08-21 | 2020-10-22 | Janssen Pharmaceutica Nv | Anticuerpos para haptenos de quetiapina y uso de los mismos |
| CA2882490A1 (en) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc. | Antibodies to paliperidone and use thereof |
| EP3462173B1 (en) | 2012-08-21 | 2021-03-31 | Janssen Pharmaceutica NV | Antibodies to risperidone 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 |
| EP3390455A1 (en) | 2015-12-17 | 2018-10-24 | Janssen Pharmaceutica NV | Antibodies to quetiapine and use thereof |
| 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 |
| CN110938082A (zh) * | 2019-10-30 | 2020-03-31 | 杭州博拓生物科技股份有限公司 | 一种奥氮平人工抗原及其制备方法 |
| CN110950808A (zh) * | 2019-10-30 | 2020-04-03 | 杭州博拓生物科技股份有限公司 | 一种氯氮平人工抗原及其制备方法 |
| 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 |
| CN114685477B (zh) * | 2020-12-25 | 2023-11-17 | 长沙博源医疗科技有限公司 | 一种利奈唑胺衍生物、免疫原、抗利奈唑胺特异性抗体及其制备方法与应用 |
| CN114685527B (zh) * | 2020-12-25 | 2024-03-05 | 长沙博源医疗科技有限公司 | 一种奥氮平衍生物、免疫原、抗奥氮平特异性抗体及其制备方法与应用 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022780A (en) | 1973-03-06 | 1977-05-10 | Imperial Chemical Industries Limited | Process for the manufacture of indole derivatives |
| US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
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| EP0576095B1 (en) * | 1992-06-26 | 1999-01-27 | Johnson & Johnson Clinical Diagnostics, Inc. | Immunoassays with labeled thyronine hapten analogues |
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| AR054181A1 (es) * | 2004-08-26 | 2007-06-06 | Nicholas Piramal India Ltd | Prodrogas que contienen enlaces bio-divisibles. composiiciones farmaceuticas |
| 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 |
| 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 |
| NZ722096A (en) | 2011-12-15 | 2016-11-25 | Alkermes Pharma Ireland Ltd | Prodrugs of secondary amine compounds |
| TR201816378T4 (tr) * | 2012-08-21 | 2018-11-21 | Janssen Pharmaceutica Nv | Olanzapin haptenleri. |
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| AU2013306018B2 (en) | 2017-08-10 |
| JP2019034955A (ja) | 2019-03-07 |
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| JP6423490B2 (ja) | 2018-11-14 |
| US20140213766A1 (en) | 2014-07-31 |
| ES3043017T3 (en) | 2025-11-24 |
| CA2882454C (en) | 2020-08-11 |
| EP2888269B1 (en) | 2018-10-24 |
| JP2017222671A (ja) | 2017-12-21 |
| WO2014031587A1 (en) | 2014-02-27 |
| JP6763000B2 (ja) | 2020-09-30 |
| CN104854110A (zh) | 2015-08-19 |
| CN104854110B (zh) | 2016-12-28 |
| HK1211933A1 (en) | 2016-06-03 |
| EP3492473B1 (en) | 2025-07-30 |
| AU2013306018A1 (en) | 2015-03-12 |
| JP6171014B2 (ja) | 2017-07-26 |
| TR201816378T4 (tr) | 2018-11-21 |
| EP2888269A1 (en) | 2015-07-01 |
| EP3492473A1 (en) | 2019-06-05 |
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