BR0209836A - 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 - Google Patents

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

Info

Publication number
BR0209836A
BR0209836A BR0209836-9A BR0209836A BR0209836A BR 0209836 A BR0209836 A BR 0209836A BR 0209836 A BR0209836 A BR 0209836A BR 0209836 A BR0209836 A BR 0209836A
Authority
BR
Brazil
Prior art keywords
dkk
modulate
lrp5
lrp6
hbm
Prior art date
Application number
BR0209836-9A
Other languages
Portuguese (pt)
Inventor
Kristina Allen
Anthony Anisowicz
Bheem M Bhat
Veronique Damagnez
John Allen Robinson
Paul J Yaworsky
Original Assignee
Genome Therapeutics Corp
Wyeth 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
Application filed by Genome Therapeutics Corp, Wyeth Corp filed Critical Genome Therapeutics Corp
Publication of BR0209836A publication Critical patent/BR0209836A/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

"MéTODOS PARA REGULAR A ATIVIDADE DE LRP5, LRP6 OU HBM EM UM PACIENTE, E DO CAMINHO DKK-WNT EM UM PACIENTE, PARA MODULAR A MASSA óSSEA E OS NìVEIS DE LIPìDEO EM UM PACIENTE, PARA DIAGNOSTICAR A MASSA óSSEA ALTA OU BAIXA E/OU OS NìVEIS DE LIPìDEO ALTOS OU BAIXOS EM UM PACIENTE, PARA TRIAR UM COMPOSTO QUE MODULA A INTERAçãO DE DKK COM LRP5, LRP6, HBM OU UM FRAGMENTO DE LIGAçãO DE DKK DE LRP5, LRP6 OU HBM, E DE DKK COM UMA PROTEìNA QUE INTERAGE COM A DKK, COMPOSIçãO, COMPOSIçãO FARMACêUTICA, MéTODOS PARA IDENTIFICAR COMPOSTOS QUE MODULEM AS INTERAçõES DA DKK E LRP5/LRP6/HBM, E PARA IDENTIFICAR PARCEIROS DE LIGAçãO PARA UMA PROTEìNA DE DKK, áCIDO NUCLEICO QUE CODIFICA UM APTâMERO PEPTìDICO DA PROTEìNA QUE INTERAGE COM DKK, VETOR, MéTODO PARA DETECTAR UMA ATIVIDADE MODULADORA DE UM COMPOSTO, TRANSGêNICO, MéTODO PARA IDENTIFICAR COMPOSTOS POTENCIAIS QUE MODULEM A ATIVIDADE DA DKK, APTâMERO PEPTìDICO, ANTICORPO OU FRAGMENTO DE ANTICORPO, E, MéTODOS PARA IDENTIFICAR PROTEìNAS QUE INTERAGEM COM A DKK MODULANDO A INTERAçãO DA DKK COM O CAMINHO DE SINALIZAçãO WNT, PARA IDENTIFICAR COMPOSTOS QUE MODULEM A INTERAçãO DA DKK COM O CAMINHO DE SINALIZAçãO WNT, PARA TESTAR COMPOSTOS QUE MODULAM A ATIVIDADE MEDIADA PELA DKK EM UM MAMìFERO, E PARA TRIAR CONWOSTOS OU COMPOSIçõES QUE MODULAM A INTERAçãO DA DKK E UMA PROTEìNA QUE INTERAGE COM A DKK". A presente invenção fornece reagentes, compostos, composições e métodos que dizem respeito a novas interações do domínio extracelular de LRP5, HBM (uma variante de LRP5) e/ou LRP6 com Dkk incluindo Dkk-1. Os vários ácidos nucléicos, polipeptídeos, anticorpos, métodos de ensaio, métodos de diagnóstico e métodos de tratamento da presente invenção estão relacionados e colidem com Dkk, LRP5, LRP6, HBM e sinalização Wnt. Dkk, LRP5, LRP6, HBM e Wnt estão implicados na sinalização celular óssea e lipídica. Assim, a presente invenção fornece reagentes e métodos para modular os níveis de lipídeo e/ou a massa óssea e é útil no tratamento e diagnóstico de níveis lipídicos anormais e distúrbios de massa óssea, tais como a osteoporose."METHODS FOR ADJUSTING THE ACTIVITY OF LRP5, LRP6 OR HBM IN A PATIENT, AND THE DKK-WNT PATH IN A PATIENT, TO MODULATE BONE MASS AND LEVEL BONE / HIGH BONE / DIAGNOSTIC DIAGNOSIS OR HIGH OR LOW LIPID LEVELS IN A PATIENT, TO CREATE A COMPOUND THAT MODULATES DKK INTERACTION WITH LRP5, LRP6, HBM OR A DKK LINK FRAGMENT OF LRP5, LRP6 OR HBM, AND A PROTEK WITH DIKK WITH DKK, COMPOSITION, PHARMACEUTICAL COMPOSITION, METHODS FOR IDENTIFYING COMPOUNDS THAT MODULE DKK AND LRP5 / LRP6 / HBM INTERACTIONS, AND FOR IDENTIFYING PARKING PARTNERS FOR A NUCLET PROKIN DUCKY PROKIN CODE DKK, VECTOR, METHOD FOR DETECTING A TRANSGENIC COMPOUND MODULATOR ACTIVITY, METHOD FOR IDENTIFYING POTENTIAL COMPOUNDS THAT MODULE PEKTIDIC APTITUDE, ANTIBODY OR FRAGMENT, AND ANTIBODY IDENTITY GET PROTEINS THAT INTERACT WITH DKK BY MODULATING DKK INTERACTION WITH THE WNT SIGNALING WAY TO IDENTIFY COMPOUNDS THAT MODULE DKK INTERACTION TO TEST COMPOUNDS THAT DAMAGE A MK DIFFERING AND COMPACTING A DKK TO CREATE CONWOSTS OR COMPOSITIONS THAT MODULATE DKK INTERACTION AND A PROTEIN INTERACTING WITH DKK ". The present invention provides reagents, compounds, compositions and methods that relate 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 treatment methods of the present invention are related and collide with Dkk, LRP5, LRP6, HBM, and Wnt signaling. Dkk, LRP5, LRP6, HBM and Wnt are implicated in bone and lipid cell signaling. Thus, the present invention provides reagents and methods for modulating lipid levels and / or bone mass and is useful in treating and diagnosing abnormal lipid levels and bone mass disorders, such as osteoporosis.

BR0209836-9A 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 BR0209836A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US29131101P 2001-05-17 2001-05-17
US35305802P 2002-02-01 2002-02-01
US36129302P 2002-03-04 2002-03-04
PCT/US2002/015982 WO2002092015A2 (en) 2001-05-17 2002-05-17 Reagents and methods for modulating dkk-mediated interactions

Publications (1)

Publication Number Publication Date
BR0209836A true BR0209836A (en) 2004-12-07

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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

Country Status (7)

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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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CA2446582A1 (en) 2002-11-21
WO2002092015A2 (en) 2002-11-21
IL158750A0 (en) 2004-05-12
WO2002092015A3 (en) 2003-10-23
JP2005512508A (en) 2005-05-12
JP2009142274A (en) 2009-07-02
EP1395285A4 (en) 2005-06-01
EP1395285A2 (en) 2004-03-10
AU2002342734B2 (en) 2007-07-26

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