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
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
Original Assignee
Genome Therapeutics Corp
Wyeth Corp
Kristina Allen
Anthony Anisowicz
Bheem M Bhat
Veronique Damagnez
John Allen Robinson
Paul J Yaworsky
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
Application filed by Genome Therapeutics Corp, Wyeth Corp, Kristina Allen, Anthony Anisowicz, Bheem M Bhat, Veronique Damagnez, John Allen Robinson, Paul J Yaworsky filed Critical Genome Therapeutics Corp
Priority to JP2002588934A priority Critical patent/JP2005512508A/en
Priority to BR0209836-9A priority patent/BR0209836A/en
Priority to IL15875002A priority patent/IL158750A0/en
Priority to EP02744162A priority patent/EP1395285A4/en
Priority to US10/182,936 priority patent/US20040038860A1/en
Priority to CA002446582A priority patent/CA2446582A1/en
Priority to AU2002342734A priority patent/AU2002342734B2/en
Publication of WO2002092015A2 publication Critical patent/WO2002092015A2/en
Publication of WO2002092015A3 publication Critical patent/WO2002092015A3/en
Priority to US11/655,924 priority patent/US7700101B2/en

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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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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

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 WO2002092015A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2002588934A JP2005512508A (en) 2001-05-17 2002-05-17 Reagents and methods for modulating Dkk-mediated interactions
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
IL15875002A IL158750A0 (en) 2001-05-17 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 dkk-mediated interactions
US10/182,936 US20040038860A1 (en) 2002-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
CA002446582A CA2446582A1 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions
AU2002342734A AU2002342734B2 (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 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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DE60235524D1 (en) 2002-04-17 2010-04-15 Deutsches Krebsforsch Method for screening a substance for modulating the wnt signal cascade.
US8124087B2 (en) 2002-12-05 2012-02-28 Board Of Trustees Of The University Of Arkansas Methods of controlling bone loss by inhibiting DKK1
EP1913952B1 (en) * 2002-12-05 2011-03-09 The Board Of Trustees Of The University Of Arkansas Molecular determinants of myeloma bone disease and uses thereof
US7642238B2 (en) * 2002-12-05 2010-01-05 Shaughnessy John D Molecular determinants of myeloma bone disease and uses thereof
EP1636385A4 (en) * 2003-06-24 2010-06-02 Mirus Bio Corp 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
WO2005049797A2 (en) 2003-11-17 2005-06-02 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
CA2574881C (en) 2004-08-04 2013-01-08 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
WO2008097510A1 (en) * 2007-02-08 2008-08-14 Merck & Co., Inc. Antibodies specific for dkk-1
CN101951954A (en) * 2007-11-02 2011-01-19 诺瓦提斯公司 Molecules and methods for modulating low-density-lipoprotein receptor-related protein 6 (LRP6)
AR075989A1 (en) 2009-04-10 2011-05-11 Lilly Co Eli ANTIBODY DKK -1 (DICKKOPF-1) HUMAN DESIGNED BY ENGINEERING
KR20120117621A (en) * 2009-05-07 2012-10-24 노파르티스 아게 Compositions and methods of use for binding molecules to dickkopf-1 or dickkopf-4 or both
PE20120475A1 (en) * 2009-05-12 2012-05-05 Pfizer SPECIFIC ANTIBODIES FOR DKK-1
CA2790200A1 (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
KR101899835B1 (en) 2010-03-24 2018-09-19 제넨테크, 인크. Anti-lrp6 antibodies
KR20130066631A (en) 2010-05-06 2013-06-20 노파르티스 아게 Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies
EP4234698A3 (en) 2010-05-06 2023-11-08 Novartis AG Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies
WO2013067355A1 (en) 2011-11-04 2013-05-10 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
US20200179510A1 (en) * 2017-03-24 2020-06-11 Yale University Low density lipoprotein receptor related protein 5 inhibition suppresses tumor formation
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Also Published As

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

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