AU2002217310B2 - Materials and methods relating to protein aggregation in neurodegenerative disease - Google Patents

Materials and methods relating to protein aggregation in neurodegenerative disease Download PDF

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Publication number
AU2002217310B2
AU2002217310B2 AU2002217310A AU2002217310A AU2002217310B2 AU 2002217310 B2 AU2002217310 B2 AU 2002217310B2 AU 2002217310 A AU2002217310 A AU 2002217310A AU 2002217310 A AU2002217310 A AU 2002217310A AU 2002217310 B2 AU2002217310 B2 AU 2002217310B2
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Prior art keywords
tau
protein
adp
aggregation
membrane
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AU2002217310A
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AU2002217310A1 (en
Inventor
Charles Robert Harrington
David Horsley
Janet Elizabeth Rickard
Karsten Stamer
Franz Theuring
Claude Michel Wischik
Claudia Zabke
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Wista Laboratories Ltd
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Wista Laboratories Ltd
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • 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
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • 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
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • 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
    • 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
    • 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
    • A01K2217/20—Animal model comprising regulated expression system
    • 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
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0306—Animal model for genetic diseases
    • A01K2267/0312—Animal model for Alzheimer's disease
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0306—Animal model for genetic diseases
    • A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Environmental Sciences (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • General Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Neurosurgery (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Husbandry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Plant Pathology (AREA)
  • Public Health (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
AU2002217310A 2001-01-03 2002-01-02 Materials and methods relating to protein aggregation in neurodegenerative disease Expired AU2002217310B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0100119.7 2001-01-03
GBGB0100119.7A GB0100119D0 (en) 2001-01-03 2001-01-03 Materials and methods relating to protein aggregation in neurodegenerative disease
PCT/GB2002/000005 WO2002059150A2 (en) 2001-01-03 2002-01-02 Materials and methods relating to protein aggregation in neurodegenerative disease

Publications (2)

Publication Number Publication Date
AU2002217310A1 AU2002217310A1 (en) 2003-02-06
AU2002217310B2 true AU2002217310B2 (en) 2007-09-20

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ID=9906201

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AU2002217310A Expired AU2002217310B2 (en) 2001-01-03 2002-01-02 Materials and methods relating to protein aggregation in neurodegenerative disease

Country Status (11)

Country Link
US (1) US7834237B2 (https=)
EP (1) EP1348029B1 (https=)
JP (1) JP4580618B2 (https=)
AT (1) ATE548453T1 (https=)
AU (1) AU2002217310B2 (https=)
CA (1) CA2433535C (https=)
DK (1) DK1348029T3 (https=)
ES (1) ES2382457T3 (https=)
GB (1) GB0100119D0 (https=)
PT (1) PT1348029E (https=)
WO (1) WO2002059150A2 (https=)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9506197D0 (en) 1995-03-27 1995-05-17 Hoffmann La Roche Inhibition of tau-tau association.
GB0101049D0 (en) 2001-01-15 2001-02-28 Univ Aberdeen Materials and methods relating to protein aggregation in neurodegenerative disease
GB0104685D0 (en) * 2001-02-26 2001-04-11 Leuven K U Res & Dev Tau-opathy model
GB0106953D0 (en) 2001-03-20 2001-05-09 Univ Aberdeen Neufofibrillary labels
GB0117326D0 (en) 2001-07-16 2001-09-05 Univ Aberdeen Napthoquinone-type inhibitors of protein aggregation
CN100572392C (zh) * 2002-07-12 2009-12-23 阿克松神经科学研究和发展股份有限公司 截短tau蛋白
EP1516930A1 (en) * 2003-09-16 2005-03-23 Georg-August Universität Göttingen Cellular model of tauopathies for lead identification and drug discovery
ATE442588T1 (de) * 2004-03-31 2009-09-15 Anges Mg Inc Testverfahren zur identifizierung eines kandidatenarzneistoffs
JP4814875B2 (ja) 2004-05-11 2011-11-16 アキシオジェネシス エージー ｉｎｖｉｔｒｏ分化細胞に基づく薬物発見のための検定
CN101084204B (zh) 2004-09-23 2012-12-05 卫思道制药有限公司 包括亚甲蓝(mtc)在内的二氨基吩噻嗪鎓化合物的化学合成和纯化方法
US9802992B2 (en) * 2005-12-06 2017-10-31 Tokyo Metropolitan Institute Of Medical Science Cell into which protein, which can serve as polymerization nucleus of protein polymer, or polymer thereof is introduced, and method for production of the cell
EP2013191B3 (en) 2006-03-29 2019-02-27 Wista Laboratories Ltd. 3,7-diamino-10h-phenothiazine salts and their use
PL2004155T3 (pl) 2006-03-29 2018-08-31 Wista Laboratories Ltd. Inhibitory agregacji białek
CA3027974C (en) 2007-10-03 2022-03-15 Wista Laboratories Ltd. Therapeutic use of diaminophenothiazines
US8703137B2 (en) 2011-01-31 2014-04-22 Intellect Neurosciences Inc. Treatment of tauopathies
EA025033B1 (ru) 2011-02-11 2016-11-30 Уиста Лэборэтэриз Лтд. Диаминиевые соли фенотиазина и их применение
EP2709728B1 (en) 2011-05-20 2019-01-23 Oligomerix, Inc. Tau protease methods of use
KR102592614B1 (ko) 2016-07-25 2023-10-24 위스타 레보레이토리스 리미티드 디아미노페노티아진 (diaminophenothiazines)의 투여 및 투여량 (dosage)
EP3668891B1 (en) * 2017-08-16 2023-07-26 Lgv1 S.R.L. Vtft isoform of a bpifb4 protein for use in neuronal deseases and injuries
WO2020201828A1 (en) 2019-04-05 2020-10-08 Tauc3 Biologics Limited Anti-tauc3 antibodies and uses thereof
GB201909493D0 (en) 2019-07-01 2019-08-14 Wista Lab Ltd Therapeutic interactions
GB201909454D0 (en) 2019-07-01 2019-08-14 Wista Lab Ltd Enhancers
GB201909506D0 (en) 2019-07-02 2019-08-14 Wista Lab Ltd Synaptopathies
CN113943766B (zh) * 2021-11-26 2024-01-26 守正创新生物科技(天津)有限公司 一种抗糖化寡肽-5（AdP）的制备及其应用

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE569430A (https=) * 1957-07-17
GB8724412D0 (en) 1987-10-19 1987-11-25 Medical Res Council Protein
US5571666A (en) * 1988-10-28 1996-11-05 Oklahoma Medical Research Foundation Thiazine dyes used to inactivate HIV in biological fluids
JPH0725786A (ja) 1990-05-16 1995-01-27 Univ Rockefeller アルツハイマー病を伴うアミロイドーシスの治療
US5912410A (en) * 1990-06-15 1999-06-15 Scios Inc. Transgenic non-human mice displaying the amyloid-forming pathology of alzheimer's disease
JP3210336B2 (ja) 1991-07-10 2001-09-17 ミネソタ マイニング アンド マニュファクチャリング カンパニー フルオロケミカル撥水性および撥油性処理組成物
WO1993003369A1 (en) 1991-08-01 1993-02-18 Voorheis Paul H Diagnostic method for alzheimer's disease
ATE398176T1 (de) 1991-12-06 2008-07-15 Max Planck Gesellschaft Phosphorylierungsepitope aus dem tau-protein zur diagnose und behandlung der alzheimer-krankheit
GB9316727D0 (en) 1993-08-12 1993-09-29 Inst Of Psychiatry Models of alzheimers's disease
GB9317193D0 (en) 1993-08-18 1993-10-06 Zeneca Ltd Method
FR2722695B1 (fr) 1994-07-22 1997-04-25 Demic Lab Sa Ustensile de badigeonnage cutane par frottement a usage medical
EP0778773A1 (en) 1994-08-08 1997-06-18 Albert Einstein College Of Medicine Of Yeshiva University Methods for treating and/or preventing alzheimer's disease using phenothiazines and/or thioxanthenes
DE4430091A1 (de) 1994-08-25 1996-02-29 Bayer Ag Verwendung von N-substituierten Phenothiazinen
GB9506197D0 (en) 1995-03-27 1995-05-17 Hoffmann La Roche Inhibition of tau-tau association.
US5804601A (en) 1995-04-10 1998-09-08 Takeda Chemical Industries, Ltd. Aromatic hydroxamic acid compounds, their production and use
US5898094A (en) * 1996-10-21 1999-04-27 University Of South Florida Transgenic mice expressing APPK670N,M671L and a mutant presenilin transgenes
WO1999062548A1 (en) * 1998-06-01 1999-12-09 Advanced Research And Technology Institute Methods and compositions for diagnosing tauopathies
DE19920514A1 (de) * 1999-05-05 2000-11-16 Boehringer Ingelheim Pharma Methoden zur Auffindung von Proteasen, die spezifisch membrangebundene Substrate spalten
AU2001229619A1 (en) 2000-01-21 2001-07-31 Pharmacia And Upjohn Company Transgenic mouse model of human neurodegenerative disease
JP2001352860A (ja) 2000-06-15 2001-12-25 Inst Of Physical & Chemical Res 老年期痴呆症で生じる神経原線維変化を示すマウス
GB0101049D0 (en) 2001-01-15 2001-02-28 Univ Aberdeen Materials and methods relating to protein aggregation in neurodegenerative disease
GB0106953D0 (en) 2001-03-20 2001-05-09 Univ Aberdeen Neufofibrillary labels
GB0117326D0 (en) 2001-07-16 2001-09-05 Univ Aberdeen Napthoquinone-type inhibitors of protein aggregation
US20030217370A1 (en) * 2002-05-16 2003-11-20 Giasson Benoit I. Transgenic animal expressing alpha-synuclein and uses thereof
US6953974B2 (en) * 2003-08-26 2005-10-11 Texas Instruments Incorporated EEPROM device and method for providing lower programming voltage
GB0322756D0 (en) 2003-09-29 2003-10-29 Univ Aberdeen Methods of chemical synthesis
AU2005286235C1 (en) 2004-09-23 2013-08-22 TauRx Therapeutics Management Ltd Methods of chemical synthesis and purification of diaminophenothiazinium compounds including Methylthioninium Chloride (MTC)

Also Published As

Publication number Publication date
EP1348029B1 (en) 2012-03-07
CA2433535A1 (en) 2002-08-01
CA2433535C (en) 2011-02-15
WO2002059150A2 (en) 2002-08-01
US7834237B2 (en) 2010-11-16
WO2002059150A3 (en) 2002-12-05
PT1348029E (pt) 2012-06-15
HK1056574A1 (en) 2004-02-20
ES2382457T3 (es) 2012-06-08
ATE548453T1 (de) 2012-03-15
JP4580618B2 (ja) 2010-11-17
GB0100119D0 (en) 2001-02-14
EP1348029A2 (en) 2003-10-01
US20040078835A1 (en) 2004-04-22
DK1348029T3 (da) 2012-05-29
JP2004531224A (ja) 2004-10-14

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