WO2000017334A3 - Analysis of ligand activated nuclear receptors i(in vivo) - Google Patents

Analysis of ligand activated nuclear receptors i(in vivo) Download PDF

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Publication number
WO2000017334A3
WO2000017334A3 PCT/IB1999/001682 IB9901682W WO0017334A3 WO 2000017334 A3 WO2000017334 A3 WO 2000017334A3 IB 9901682 W IB9901682 W IB 9901682W WO 0017334 A3 WO0017334 A3 WO 0017334A3
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WO
WIPO (PCT)
Prior art keywords
nuclear receptors
vivo
analysis
ligands
present
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.)
Ceased
Application number
PCT/IB1999/001682
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French (fr)
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WO2000017334A2 (en
WO2000017334A9 (en
Inventor
Ludmila Solomin
De Urquiza Alexander Mata
Thomas Perlmann
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Priority to EP99969436A priority Critical patent/EP1115853A2/en
Priority to AU59941/99A priority patent/AU5994199A/en
Publication of WO2000017334A2 publication Critical patent/WO2000017334A2/en
Publication of WO2000017334A3 publication Critical patent/WO2000017334A3/en
Anticipated expiration legal-status Critical
Publication of WO2000017334A9 publication Critical patent/WO2000017334A9/en
Ceased legal-status Critical Current

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    • 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
    • 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
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70567—Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • 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
    • 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
    • A01K2267/0393—Animal model comprising a reporter system for screening tests
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
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    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
    • C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Environmental Sciences (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Plant Pathology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The present invention relates to detection of ligands for nuclear receptors in vivo. In particular, the present invention provides transgenic constructs and transgenic animals, as well as assays using the same to detect ligands for nuclear receptors in transgenic animals. The transgenic constructs, transgenic animals and assays of the present invention are useful for identification and isolation of ligands for orphan receptors. In addition, the invention is useful for analyzing pharmacological properties of natural and synthetic ligands for nuclear receptors.
PCT/IB1999/001682 1998-09-23 1999-09-23 Analysis of ligand activated nuclear receptors i(in vivo) Ceased WO2000017334A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP99969436A EP1115853A2 (en) 1998-09-23 1999-09-23 Analysis of ligand activated nuclear receptors in vivo
AU59941/99A AU5994199A (en) 1998-09-23 1999-09-23 Analysis of ligand activated nuclear receptors (in vivo)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10148498P 1998-09-23 1998-09-23
US60/101,484 1998-09-23

Publications (3)

Publication Number Publication Date
WO2000017334A2 WO2000017334A2 (en) 2000-03-30
WO2000017334A3 true WO2000017334A3 (en) 2000-09-21
WO2000017334A9 WO2000017334A9 (en) 2001-07-05

Family

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Family Applications (1)

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PCT/IB1999/001682 Ceased WO2000017334A2 (en) 1998-09-23 1999-09-23 Analysis of ligand activated nuclear receptors i(in vivo)

Country Status (3)

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EP (1) EP1115853A2 (en)
AU (1) AU5994199A (en)
WO (1) WO2000017334A2 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6548739B2 (en) * 1999-06-18 2003-04-15 City Of Hope Method for activating peroxisome proliferator activated receptor-γ
WO2002072874A1 (en) * 2001-03-14 2002-09-19 Fujisawa Pharmaceutical Co., Ltd. METHOD OF SCREENING HNF4α AGONIST
FI116851B (en) * 2001-05-03 2006-03-15 Fit Biotech Oyj Plc Expression vector, its uses and process for its preparation and products containing it
EP1465882B1 (en) 2001-12-21 2011-08-24 X-Ceptor Therapeutics, Inc. Hetrocyclic modulators of nuclear receptors
US7998986B2 (en) 2001-12-21 2011-08-16 Exelixis Patent Company Llc Modulators of LXR
US7482366B2 (en) 2001-12-21 2009-01-27 X-Ceptor Therapeutics, Inc. Modulators of LXR
WO2004053124A1 (en) * 2002-12-06 2004-06-24 Shionogi & Co., Ltd. Method of screening remedy or preventive for diabetes
WO2004058717A1 (en) 2002-12-20 2004-07-15 X-Ceptor Therapeutics, Inc. Isoquinolinone derivatives and their use as therapeutic agents
WO2005071418A2 (en) * 2003-10-29 2005-08-04 Evotec Neurosciences Gmbh Diagnostic and therapeutic use of the human dax- 1 gene and protein for neurodegenerative diseases
KR101363278B1 (en) 2005-06-27 2014-02-21 엑셀리시스 페이턴트 컴퍼니 엘엘씨 Imidazole based lxr modulators
US7790745B2 (en) 2005-10-21 2010-09-07 Bristol-Myers Squibb Company Tetrahydroisoquinoline LXR Modulators
US7741317B2 (en) 2005-10-21 2010-06-22 Bristol-Myers Squibb Company LXR modulators
MY153958A (en) 2009-05-28 2015-04-30 Exelixis Patent Co Llc Lxr modulators
TW201242953A (en) 2011-03-25 2012-11-01 Bristol Myers Squibb Co Imidazole prodrug LXR modulators
MX2014015205A (en) 2012-06-14 2015-08-14 Ambrx Inc Anti-psma antibodies conjugated to nuclear receptor ligand polypeptides.
JP6442475B2 (en) 2013-03-15 2018-12-19 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ LXR regulator

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999005292A1 (en) * 1997-07-22 1999-02-04 Chugai Seiyaku Kabushiki Kaisha Method for gene screening with the use of nuclear receptors

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999005292A1 (en) * 1997-07-22 1999-02-04 Chugai Seiyaku Kabushiki Kaisha Method for gene screening with the use of nuclear receptors

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BALKAN W ET AL.: "Transgenic indicator mice for studying activated retinoic acid receptors during development", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 89, April 1992 (1992-04-01), WASHINGTON US, pages 3347 - 3351, XP002134850 *
LEMON B D ET AL: "Selective effects of ligands on vitamin D3 receptor- and retinoid receptor-mediated gene activation in vivo", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 3, March 1996 (1996-03-01), WASHINGTON US, pages 1006 - 1016, XP002134851 *
SOLOMIN L ET AL.: "Retinoid-X receptor signalling in the developing spinal cord", NATURE, vol. 395, 24 September 1998 (1998-09-24), LONDON GB, pages 398 - 402, XP002134853 *
WANG Y ET AL: "Ligand-inducible and liver-specific target gene expression in transgenic mice", NATURE BIOTECHNOLOGY., vol. 15, no. 3, March 1997 (1997-03-01), NATURE PUBLISHING, US, pages 239 - 243, XP002134852, ISSN: 1087-0156 *

Also Published As

Publication number Publication date
WO2000017334A2 (en) 2000-03-30
WO2000017334A9 (en) 2001-07-05
AU5994199A (en) 2000-04-10
EP1115853A2 (en) 2001-07-18

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