CA2246751A1 - Human metabotropic glutamate receptor - Google Patents
Human metabotropic glutamate receptor Download PDFInfo
- Publication number
- CA2246751A1 CA2246751A1 CA002246751A CA2246751A CA2246751A1 CA 2246751 A1 CA2246751 A1 CA 2246751A1 CA 002246751 A CA002246751 A CA 002246751A CA 2246751 A CA2246751 A CA 2246751A CA 2246751 A1 CA2246751 A1 CA 2246751A1
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- Prior art keywords
- nucleic acid
- amino acid
- seq
- sequence
- metabotropic glutamate
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- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Psychology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/604,298 US6084084A (en) | 1996-02-21 | 1996-02-21 | Human metabotropic glutamate receptor |
| US08/604,298 | 1996-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2246751A1 true CA2246751A1 (en) | 1997-12-24 |
Family
ID=24419059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002246751A Abandoned CA2246751A1 (en) | 1996-02-21 | 1997-02-20 | Human metabotropic glutamate receptor |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6084084A (enExample) |
| EP (1) | EP0882065B1 (enExample) |
| JP (1) | JP2000506392A (enExample) |
| AT (1) | ATE369385T1 (enExample) |
| AU (1) | AU719841B2 (enExample) |
| CA (1) | CA2246751A1 (enExample) |
| DE (1) | DE69737990T2 (enExample) |
| ES (1) | ES2292193T3 (enExample) |
| IL (2) | IL125711A0 (enExample) |
| WO (1) | WO1997048724A2 (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US5521297A (en) * | 1993-06-04 | 1996-05-28 | Salk Institute Biotechnology/Industrial Associates | Nucleic acids encoding human metabotropic glutamate receptors |
| US5981195A (en) * | 1995-07-26 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors |
| US6221609B1 (en) * | 1996-07-03 | 2001-04-24 | Eli Lilly And Company | Isolate nucleic acid encoding human MGLUR8 |
| EP1066325A1 (en) * | 1998-04-03 | 2001-01-10 | Nps Pharmaceuticals, Inc. | G-protein fusion receptors and chimeric gaba b? receptors |
| US7262280B1 (en) | 1998-04-03 | 2007-08-28 | Nps Pharmaceuticals, Inc. | G-protein fusion receptors and constructs encoding same |
| EP1662255A3 (en) * | 1998-08-18 | 2006-09-13 | The Johns Hopkins University School Of Medicine | Homer interacting proteins |
| WO2000011204A2 (en) * | 1998-08-18 | 2000-03-02 | The Johns Hopkins University School Of Medicine | Homer interacting proteins |
| CA2341018C (en) * | 1998-08-31 | 2012-07-31 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Polypeptides and polynucleotides from coagulase-negative staphylococci |
| US20030166554A1 (en) * | 2001-01-16 | 2003-09-04 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US20030185754A1 (en) * | 2001-01-16 | 2003-10-02 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US6620850B2 (en) * | 2001-09-19 | 2003-09-16 | University Of Florida | Materials and methods for treatment of neurological disorders involving overactivation of glutamatergic ionotropic receptors |
| WO2003054167A2 (en) * | 2001-12-20 | 2003-07-03 | Merck & Co., Inc. | Identification of novel polymorphic sites in the human mglur8 gene and uses thereof |
| MXPA04006728A (es) * | 2002-01-10 | 2005-08-19 | Osteotrophin Llc | Tratamiento de desordenes oseos con medicamentos anabolicos esqueleticos. |
| US20060252922A1 (en) * | 2002-12-04 | 2006-11-09 | Macina Roberto A | Compositions, splice variants and methods relating to colon specific genes and proteins |
| US20050186658A1 (en) * | 2003-10-17 | 2005-08-25 | Nps Pharmaceuticals, Inc. | Chimeric metabotropic glutamate receptors and uses thereof |
| WO2005073730A1 (en) * | 2004-01-31 | 2005-08-11 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human metabotropic glutamate receptor 8 (mglur8) |
| US7777016B2 (en) * | 2004-10-14 | 2010-08-17 | Carnegie Institution Of Washington | Neurotransmitter sensors and methods of using the same |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| US8889950B2 (en) * | 2006-07-28 | 2014-11-18 | The George Washington University | Repression of AtGLR3.2 increases plant biomass |
| US7424876B2 (en) * | 2006-10-06 | 2008-09-16 | Ford Global Technologies, Llc | Pushrod engine with multiple independent lash adjusters for each pushrod |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| DK2203439T3 (da) | 2007-09-14 | 2011-04-18 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituerede 4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4']-bipyridinyl-2'-oner |
| CA2707309A1 (en) | 2007-12-18 | 2009-06-25 | Acumen Pharmaceuticals, Inc. | Novel addl receptor polypeptides, polynucleotides and host cells for recombinant production |
| WO2010011404A2 (en) * | 2008-05-20 | 2010-01-28 | Eos Neuroscience, Inc. | Vectors for delivery of light-sensitive proteins and methods of use |
| AU2009289784B2 (en) | 2008-09-02 | 2012-03-22 | Addex Pharma S.A. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
| RU2512283C2 (ru) | 2008-11-28 | 2014-04-10 | Янссен Фармасьютикалз, Инк. | Производные индола и бензоксазина в качестве модуляторов метаботропных глутаматных рецепторов |
| JO2907B1 (en) | 2009-05-12 | 2015-09-15 | اديكس فرما اس ايه | Pyridine derivatives 1, 2, 4 trisolo [4, 3-A] and their uses as positive LLs for 2MGLUR receptors |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| NZ596053A (en) | 2009-05-12 | 2013-05-31 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CN103298810B (zh) | 2010-11-08 | 2016-03-16 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| ES2536433T3 (es) | 2010-11-08 | 2015-05-25 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| EA033889B1 (ru) | 2014-01-21 | 2019-12-05 | Янссен Фармацевтика Нв | Комбинация на основе лиганда sv2a и положительного аллостерического модулятора метаботропного глутаматергического рецептора 2 подтипа |
| HUE045610T2 (hu) | 2014-01-21 | 2020-01-28 | Janssen Pharmaceutica Nv | 2-es altípusú metabotróp glutamáterg receptor pozitív allosztérikus modulátorait vagy ortosztérikus agonistáit tartalmazó kombinációk és alkalmazásuk |
| RU2765242C2 (ru) | 2015-08-07 | 2022-01-27 | Имаджинаб, Инк. | Антигенсвязывающие конструкции против молекул-мишеней |
| WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
| CA3060443A1 (en) | 2017-04-19 | 2018-10-25 | Board Of Regents, The University Of Texas System | Immune cells expressing engineered antigen receptors |
| EP3755349A4 (en) | 2018-02-21 | 2021-11-17 | Board of Regents, The University of Texas System | PROCESS FOR ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS AND THEIR USES |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1311829A (en) * | 1971-02-20 | 1973-03-28 | Hayashibara Co | Sealsoning of comestibles |
| US4945050A (en) * | 1984-11-13 | 1990-07-31 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues and apparatus therefor |
| US5177011A (en) * | 1988-08-18 | 1993-01-05 | Calgene, Inc. | Plant elongation factor promoters, coding sequences and uses |
| JP2944721B2 (ja) * | 1990-08-22 | 1999-09-06 | 生化学工業株式会社 | エンドトキシンの測定剤 |
| NZ240921A (en) * | 1990-12-12 | 1994-06-27 | Zymogenetics Inc | G protein coupled glutamate receptor (neurotransmitters), recombinant production |
| ES2218531T3 (es) * | 1991-08-23 | 2004-11-16 | Nps Pharmaceuticals, Inc. | Arilalquilaminas activas sobre los receptores del calcio. |
| ES2256370T3 (es) * | 1991-08-23 | 2006-07-16 | Nps Pharmaceuticals, Inc. | Moleculas activas para el receptor de calcio. |
| IL105587A0 (en) * | 1992-05-08 | 1993-09-22 | Lilly Co Eli | Human metabotropic glutamate receptor and related dna compounds |
| EP0642589A4 (en) * | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
| US6228610B1 (en) * | 1993-09-20 | 2001-05-08 | Novartis Corporation | Human metabotropic glutamate receptor subtypes (hmR4, hmR6, hmR7) and related DNA compounds |
| US6274330B1 (en) * | 1993-12-30 | 2001-08-14 | Zymogenetics, Inc. | L-AP4 sensitive glutamate receptors |
| AU6912594A (en) * | 1994-05-16 | 1995-12-05 | Human Genome Sciences, Inc. | Neurotransmitter transporter |
| US5981195A (en) * | 1995-07-26 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors |
-
1996
- 1996-02-21 US US08/604,298 patent/US6084084A/en not_active Expired - Fee Related
-
1997
- 1997-02-20 AT AT97933988T patent/ATE369385T1/de not_active IP Right Cessation
- 1997-02-20 EP EP97933988A patent/EP0882065B1/en not_active Expired - Lifetime
- 1997-02-20 IL IL12571197A patent/IL125711A0/xx active IP Right Grant
- 1997-02-20 JP JP9540300A patent/JP2000506392A/ja active Pending
- 1997-02-20 CA CA002246751A patent/CA2246751A1/en not_active Abandoned
- 1997-02-20 DE DE69737990T patent/DE69737990T2/de not_active Expired - Fee Related
- 1997-02-20 WO PCT/US1997/009025 patent/WO1997048724A2/en not_active Ceased
- 1997-02-20 ES ES97933988T patent/ES2292193T3/es not_active Expired - Lifetime
- 1997-02-20 AU AU37156/97A patent/AU719841B2/en not_active Ceased
- 1997-03-24 US US08/823,437 patent/US6051688A/en not_active Expired - Fee Related
- 1997-03-24 US US08/823,110 patent/US6077675A/en not_active Expired - Fee Related
-
1998
- 1998-08-09 IL IL125711A patent/IL125711A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997048724A2 (en) | 1997-12-24 |
| US6084084A (en) | 2000-07-04 |
| DE69737990T2 (de) | 2008-09-11 |
| WO1997048724A3 (en) | 1998-03-26 |
| AU3715697A (en) | 1998-01-07 |
| EP0882065A2 (en) | 1998-12-09 |
| AU719841B2 (en) | 2000-05-18 |
| DE69737990D1 (de) | 2007-09-20 |
| ATE369385T1 (de) | 2007-08-15 |
| US6077675A (en) | 2000-06-20 |
| JP2000506392A (ja) | 2000-05-30 |
| US6051688A (en) | 2000-04-18 |
| IL125711A (en) | 2006-09-05 |
| EP0882065B1 (en) | 2007-08-08 |
| IL125711A0 (en) | 1999-04-11 |
| ES2292193T3 (es) | 2008-03-01 |
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| FZDE | Discontinued |