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WO2002092015A3 - Reagents and methods for modulating dkk-mediated interactions - Google Patents

Reagents and methods for modulating dkk-mediated interactions Download PDF

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Publication number
WO2002092015A3
WO2002092015A3 PCT/US2002/015982 US0215982W WO02092015A3 WO 2002092015 A3 WO2002092015 A3 WO 2002092015A3 US 0215982 W US0215982 W US 0215982W WO 02092015 A3 WO02092015 A3 WO 02092015A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
dkk
lrp5
lrp6
hbm
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/US2002/015982
Other languages
French (fr)
Other versions
WO2002092015A2 (en
Inventor
Kristina Allen
Anthony Anisowicz
Bheem M Bhat
Veronique Damagnez
John Allen Robinson
Paul J Yaworsky
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth LLC
Oscient Pharmaceuticals Corp
Original Assignee
Wyeth LLC
Genome Therapeutics Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to IL15875002A priority Critical patent/IL158750A0/en
Priority to BR0209836-9A priority patent/BR0209836A/en
Priority to CA002446582A priority patent/CA2446582A1/en
Priority to US10/182,936 priority patent/US20040038860A1/en
Priority to EP02744162A priority patent/EP1395285A4/en
Priority to AU2002342734A priority patent/AU2002342734B2/en
Application filed by Wyeth LLC, Genome Therapeutics Corp filed Critical Wyeth LLC
Priority to JP2002588934A priority patent/JP2005512508A/en
Publication of WO2002092015A2 publication Critical patent/WO2002092015A2/en
Publication of WO2002092015A3 publication Critical patent/WO2002092015A3/en
Anticipated expiration legal-status Critical
Priority to US11/655,924 priority patent/US7700101B2/en
Ceased legal-status Critical Current

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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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • 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
    • 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
    • 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
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • 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
    • A01K2227/50—Amphibians, e.g. Xenopus
    • 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
    • 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
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0362—Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Genetics & Genomics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)

Abstract

The present invention provides reagents, compounds, compositions, and methods relating to novel interactions of the extracellular domain of LRP5, HBM (a variant of LRP5), and/or LRP6 with Dkk, including Dkk-1. The various nucleic acids, polypeptides, antibodies, assay methods, diagnostic methods, and methods of treatment of the present invention are related to and impact on Dkk, LRP5, LRP6, HBM, and Wnt signaling. Dkk, LRP5, LRP6, HBM, and Wnt are implicated in bone and lipid cellular signaling. Thus, the present invention provides reagents and methods for modulating lipid levels and/or bone mass and is useful in the treatment and diagnosis of abnormal lipid levels and bone mass disorders, such as osteoporosis.
PCT/US2002/015982 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions Ceased WO2002092015A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
BR0209836-9A BR0209836A (en) 2001-05-17 2002-05-17 Method for regulating lrp5, lrp6 or hbm activity in a patient, and dkk-wnt pathway in a patient, to modulate bone mass and lipid levels in a patient, to diagnose high or low bone mass and / or high or low lipid levels in a patient to screen a compound that modulates dkk interaction with lrp5, lrp6, hbm or a dkk binding fragment of lrp5, lrp6 or hbm, and dkk with a protein that interacts with dkk, composition, pharmaceutical composition, methods for identifying compounds that modulate dkk and lrp5 / lrp6 / hbm interactions, and for identifying binding partners for a dkk protein, nucleic acid encoding a dkk-interacting peptide protein aptamer , vector, method for detecting a modulating activity of a transgenic animal compound, method for identifying potential compounds that modulate dkk activity, peptide aptamer, antibody or antibody fragment, and methods for identify dkk-interacting proteins by modulating dkk's interaction with the wnt signaling pathway, to identify compounds that modulate dkk's interaction with the wnt signaling pathway, to test compounds that modulate dkk-mediated activity in a mammal, and to screen compounds or compositions that modulate dkk interaction and a protein that interacts with dkk
CA002446582A CA2446582A1 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
US10/182,936 US20040038860A1 (en) 2002-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
EP02744162A EP1395285A4 (en) 2001-05-17 2002-05-17 REAGENTS AND METHODS FOR MODULATING INDUCED DKK INTERACTIONS
AU2002342734A AU2002342734B2 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating Dkk-mediated interactions
IL15875002A IL158750A0 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
JP2002588934A JP2005512508A (en) 2001-05-17 2002-05-17 Reagents and methods for modulating Dkk-mediated interactions
US11/655,924 US7700101B2 (en) 2001-05-17 2007-01-22 Reagents and method for modulating Dkk-mediated interactions

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US29131101P 2001-05-17 2001-05-17
US60/291,311 2001-05-17
US35305802P 2002-02-01 2002-02-01
US60/353,058 2002-02-01
US36129302P 2002-03-04 2002-03-04
US60/361,293 2002-03-04

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10/182,936 A-371-Of-International US20040038860A1 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
US11/655,924 Division US7700101B2 (en) 2001-05-17 2007-01-22 Reagents and method for modulating Dkk-mediated interactions

Publications (2)

Publication Number Publication Date
WO2002092015A2 WO2002092015A2 (en) 2002-11-21
WO2002092015A3 true WO2002092015A3 (en) 2003-10-23

Family

ID=27404041

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/015982 Ceased WO2002092015A2 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions

Country Status (7)

Country Link
EP (1) EP1395285A4 (en)
JP (2) JP2005512508A (en)
AU (1) AU2002342734B2 (en)
BR (1) BR0209836A (en)
CA (1) CA2446582A1 (en)
IL (1) IL158750A0 (en)
WO (1) WO2002092015A2 (en)

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Publication number Priority date Publication date Assignee Title
ES2342152T3 (en) 2002-04-17 2010-07-02 Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts METHOD FOR IDENTIFICATION OF A COMPOUND FOR MODULATION OF WNT SIGNAL WATERFALL.
US8124087B2 (en) * 2002-12-05 2012-02-28 Board Of Trustees Of The University Of Arkansas Methods of controlling bone loss by inhibiting DKK1
US7642238B2 (en) * 2002-12-05 2010-01-05 Shaughnessy John D Molecular determinants of myeloma bone disease and uses thereof
ES2362681T3 (en) * 2002-12-05 2011-07-11 The Board Of Trustees Of The University Of Arkansas MOLECULAR DETERMINANTS OF MYELOMA OSTEOPATHY AND USE OF THE SAME.
WO2005009346A2 (en) * 2003-06-24 2005-02-03 Mirus Corporation Inhibition of gene function by delivery of polynucleotide-based gene expression inhibitors to mammalian cells in vivo
US9046537B2 (en) 2003-09-22 2015-06-02 Enzo Biochem, Inc. Method for treating inflammation by administering a compound which binds LDL-receptor-related protein (LRP) ligand binding domain
US8367822B2 (en) 2003-09-22 2013-02-05 Enzo Therapeutics, Inc. Compositions and methods for bone formation and remodeling
US8637506B2 (en) * 2003-09-22 2014-01-28 Enzo Biochem, Inc. Compositions and methods for bone formation and remodeling
WO2005049640A2 (en) 2003-11-17 2005-06-02 Merck & Co., Inc. Rhesus monkey dickkopf-1, nucleotides encoding same, and uses thereof
US7473770B2 (en) 2003-11-17 2009-01-06 Merck & Co., Inc. Cynomolgus monkey dickkopf-4, nucleotides encoding same, and uses thereof
US9052324B2 (en) 2004-05-19 2015-06-09 Enzo Biochem, Inc. Compounds and assays for controlling Wnt activity
US7709611B2 (en) * 2004-08-04 2010-05-04 Amgen Inc. Antibodies to Dkk-1
WO2006015497A1 (en) * 2004-08-13 2006-02-16 Val-Chum, S.E.C. Methods of use of a dkk1 protein, immunogenic polypeptides thereof, nucleic acid encoding the dkk1 protein or polypeptides, or ligands thereof for detecting tumors; and for eliciting immune response against tumors
CA2677356A1 (en) 2007-02-08 2008-08-14 Zhiqiang An Antibodies specific for dkk-1
BRPI0820327A2 (en) * 2007-11-02 2020-10-06 Novartis Ag molecules and methods for protein modulation related to low density 6 lipoprotein receptor (lrp6)
AR075989A1 (en) 2009-04-10 2011-05-11 Lilly Co Eli ANTIBODY DKK -1 (DICKKOPF-1) HUMAN DESIGNED BY ENGINEERING
AU2010245833B2 (en) * 2009-05-07 2014-03-27 Novartis Ag Compositions and methods of use for binding molecules to Dickkopf-1 or Dickkopf-4 or both
RU2548817C2 (en) 2009-05-12 2015-04-20 Пфайзер Инк. BLOCKING ANTI-Dkk-1 ANTIBODIES AND APPLICATIONS THEREOF
WO2011103426A2 (en) * 2010-02-19 2011-08-25 The Board Of Regents Of The University Of Oklahoma Monoclonal antibodies that inhibit the wnt signaling pathway and methods of production and use thereof
TW201138823A (en) 2010-03-24 2011-11-16 Genentech Inc Anti-LRP6 antibodies
PH12012502406A1 (en) 2010-05-06 2013-02-18 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies
AU2011249782B2 (en) 2010-05-06 2014-10-02 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (LRP6) multivalent antibodies
TW201323442A (en) 2011-11-04 2013-06-16 Novartis Ag Low density lipoprotein-related protein 6 (LRP6)-half life extender constructs
CN107760686B (en) * 2016-08-23 2021-04-16 上海伯豪医学检验所有限公司 Aptamer of DKK-1 protein and application thereof
CN110709102A (en) * 2017-03-24 2020-01-17 耶鲁大学 Inhibition of low density lipoprotein receptor-related protein 5 suppresses tumor formation
US11033636B2 (en) 2017-05-31 2021-06-15 Boehringer Ingelheim International Gmbh Polypeptides antagonizing Wnt signaling in tumor cells

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Also Published As

Publication number Publication date
CA2446582A1 (en) 2002-11-21
JP2005512508A (en) 2005-05-12
BR0209836A (en) 2004-12-07
EP1395285A2 (en) 2004-03-10
JP2009142274A (en) 2009-07-02
EP1395285A4 (en) 2005-06-01
WO2002092015A2 (en) 2002-11-21
IL158750A0 (en) 2004-05-12
AU2002342734B2 (en) 2007-07-26

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