WO2008061020A2 - Méthodes permettant de traiter, de diagnostiquer ou de détecter un cancer - Google Patents

Méthodes permettant de traiter, de diagnostiquer ou de détecter un cancer Download PDF

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Publication number
WO2008061020A2
WO2008061020A2 PCT/US2007/084293 US2007084293W WO2008061020A2 WO 2008061020 A2 WO2008061020 A2 WO 2008061020A2 US 2007084293 W US2007084293 W US 2007084293W WO 2008061020 A2 WO2008061020 A2 WO 2008061020A2
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fzdlo
antibody
patient
cancer
modulator
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PCT/US2007/084293
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English (en)
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WO2008061020A3 (fr
WO2008061020A9 (fr
Inventor
Albert Lai
Guoying K. Yu
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Novartis Ag
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Priority to EP07871425A priority Critical patent/EP2084540A2/fr
Priority to MX2009005058A priority patent/MX2009005058A/es
Priority to CA002668714A priority patent/CA2668714A1/fr
Priority to JP2009536514A priority patent/JP2010509368A/ja
Priority to BRPI0718850-1A2A priority patent/BRPI0718850A2/pt
Priority to AU2007319360A priority patent/AU2007319360A1/en
Publication of WO2008061020A2 publication Critical patent/WO2008061020A2/fr
Publication of WO2008061020A3 publication Critical patent/WO2008061020A3/fr
Publication of WO2008061020A9 publication Critical patent/WO2008061020A9/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
    • G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
    • 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
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Definitions

  • a composition comprising a FZDlO modulator and one or more pharmaceutically acceptable carriers, wherein said FZDlO modulator has one or more of the activities selected from the group consisting of Dishevelled phosphorylation, c-Jun phosphorylation, and ⁇ -catenin phosphorylation.
  • the composition is provided wherein the composition is a sterile injectable.
  • the composition is provided wherein the FZDlO modulator is an inhibitor that decreases phosphorylation of Dishevelled, decreases phosphorylation of c-Jun, and increases phosphorylation of ⁇ -catenin.
  • the composition is provided wherein the FZDlO modulator decreases phosphorylation of Dishevelled or wherein the FZDlO modulator inhibits FZDlO binding to Dishevelled.
  • the imaging agent is 18 F, 43 K, 52 Fe, 57 Co, 67 Cu, 67 Ga, 77 Br, 87 MSr, 86 Y, 90 Y, 99 MTc, 111 In, 123 I, 125 I, 127 Cs, 129 Cs, 131 I, 132 I, 197 Hg, 203 Pb, Or 206 Bi.
  • region refers to a physically contiguous portion of the primary structure of a biomolecule. In the case of proteins, a region is defined by a contiguous portion of the amino acid sequence of that protein. In some embodiments a "region" is associated with a function of the biomolecule.
  • the modulator blocks expression of a gene product involved in cancer. In some embodiments the modulator blocks a physical interaction of two or more biomolecules involved in cancer. In some embodiments modulators of the invention induce or inhibit one or more FZDlO biological activities . In some embodiments the FZDlO modulator inhibits FZDlO expression.
  • antibodies include a fully assembled antibody, monoclonal antibody, polyclonal antibody, multispecific antibody (e.g., bispecific antibody), single chain antibody, chimeric antibody, humanized antibody, human engineered antibody, human antibody, diabody, triabody, tetrabody, minibody, linear antibody, chelating recombinant antibody, an intrabody, a nanobody, a small modular immunopharmaceutical (SMIP), an antigen-binding-domain immunoglobulin fusion protein, a camelized antibody, a VHH containing antibody, or a mutein of any one of these antibodies that comprise one or more CDR sequences of the antibody, and recombinant peptides comprising the forgoing as long as they exhibit the desired biological activity, (e.g., binding to the extracellular domain of FZDlO).
  • SMIP small modular immunopharmaceutical
  • stringent hybridization conditions refers to conditions under which a probe, primer, or oligonucleotide will hybridize to its target sequence, but to a minimal number of other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences will hybridize with specificity to their proper complements at higher temperatures. Generally, stringent conditions are selected to be about 5 0 C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium.
  • Tm thermal melting point
  • antibodies of the invention are specific for a non-conserved region of FZDlO.
  • 'Non-conserved region' refers to a region of lower homology with other members of the Frizzled family.
  • similarity to other Frizzled family members in these non- conserved regions is lower than 50%.
  • the modifier "monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler et al., Nature, 256:495 [19751, or may be made by recombinant DNA methods (see, e.g., U.S. Patent No. 4,816,567).
  • the antibodies are monoclonal antibodies.
  • Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975).
  • a hybridoma method a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the lymphocytes may be immunized in vitro.
  • the immunizing agent will typically include a FZDlO polypeptide, or fragment thereof or a fusion protein thereof.
  • Monoclonal antibody technology is used in implementing research, diagnosis and therapy.
  • Monoclonal antibodies are used in radioimmunoassays, enzyme-linked immunosorbent assays, immunocytopathology, and flow cytometry for in vitro diagnosis, and in vivo for diagnosis and immunotherapy of human disease. Waldmann, T. A. (1991) Science 252:1657-1662.
  • monoclonal antibodies have been widely applied to the diagnosis and therapy of cancer, wherein it is desirable to target malignant lesions while avoiding normal tissue. See, e.g., U.S. Pat. Nos. 4,753,894 to Frankel, et al.; 4,938,948 to Ring et al.; and 4,956,453 to Bjorn et al.
  • the fragments comprise a heavy chain variable region (VH) connected to a light- chain variable region (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites.
  • VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites.
  • sFv single-chain Fv
  • a disadvantage of CDR grafting is that it can result in a humanized antibody that has a substantially lower binding affinity than the original mouse antibody, because amino acids of the framework regions can contribute to antigen binding, and because amino acids of the CDR loops can influence the association of the two variable Ig domains.
  • the CDR grafting technique can be improved by choosing human framework regions that most closely resemble the framework regions of the original mouse antibody, and by site-directed mutagenesis of single amino acids within the framework or CDRs aided by computer modeling of the antigen binding site (e.g., Co, M. S., et al. (1994), J. Immunol. 152, 2968-2976).
  • epitope tag tagged refers to the antibody fused to an epitope tag.
  • the epitope tag polypeptide has enough residues to provide an epitope against which an antibody there against can be made, yet is short enough such that it does not interfere with activity of the antibody.
  • the epitope tag preferably is sufficiently unique so that the antibody there against does not substantially cross-react with other epitopes.
  • Suitable tag polypeptides generally have at least 6 amino acid residues and usually between about 8-50 amino acid residues (preferably between about 9-30 residues). Examples include the flu HA tag polypeptide and its antibody 12CA5 [Field et al., MoI. Cell. Biol.
  • O-linked glycosylation refers to the attachment of one of the sugars N-aceylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
  • O-linked glycosylation sites may be added to an antibody by inserting or substituting one or more serine or threonine residues to the sequence of the original antibody.
  • Another type of covalent modification of the antibody comprises linking the antibody to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, polyoxyethylated polyols, polyoxyethylated sorbitol, polyoxyethylated glucose, polyoxyethylated glycerol, polyoxyalkylenes, or polysaccharide polymers such as dextran.
  • nonproteinaceous polymers e.g., polyethylene glycol, polypropylene glycol, polyoxyethylated polyols, polyoxyethylated sorbitol, polyoxyethylated glucose, polyoxyethylated glycerol, polyoxyalkylenes, or polysaccharide polymers such as dextran.
  • nonproteinaceous polymers e.g., polyethylene glycol, polypropylene glycol, polyoxyethylated polyols, polyoxyethylated sorb
  • the subject's cells are removed, the nucleic acid is introduced into these cells, and the modified cells are returned to the subject either directly or, for example, encapsulated within porous membranes which are implanted into the patient. See, e.g. U.S. Pat. Nos. 4,892,538 and 5,283,187.
  • nucleic acids are introduced into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host.
  • Selective modulators may include, for example, antibodies and other proteins, peptides, or organic molecules which specifically bind to FZDlO polypeptides or to a nucleic acid encoding a FZDlO polypeptide. Modulators of FZDlO activity will be therapeutically useful in treatment of diseases and physiological conditions in which normal or aberrant activity of FZDlO polypeptide is involved.
  • Anti-FZDIO antibodies may be administered in their "naked” or unconjugated form, or may be conjugated directly to other therapeutic or diagnostic agents, or may be conjugated indirectly to carrier polymers comprising such other therapeutic or diagnostic agents.
  • WO2005/044294 discloses that IL- 2 may be administered in combination with a n antibody that binds to an antigen expressed on cancerous cells (e.g., CD40) to improve ADCC-mediated anti-tumor activity of the antibody.
  • Monoclonal antibody ADCC activity may arise from activity from the neutrophils and monocytes/macrophage population. See, for example, Hernandez-Ilizaliturri et al. (2003) Clin. Cancer Res. 9 (16, Pt 1): 5866-5873; and Uchida et al. (2004) J. Exp. Med. 199 (12): 1659- 1669).
  • IL-2 is known to activate these cell populations, one embodiment of the present invention provides combination therapy of the antagonist anti-FZDIO antibody with IL-2 or biologically active variant thereof may improve ADCC-mediated anti-tumor activity of the antibody.
  • the FZDlO modulator is an oligonucleotide having a sequence selected from the group consisting of SEQ ID NOs: 3-22 liiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii
  • Example 6 Immunohistochemistry analyses of FZDlO on lung tumor microarray (TMA) and commercial multi-tumor TMA [000363] Tissue sections were deparaffinized and antigen retrieval was performed on a

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Abstract

Cette invention concerne, entre autres, des méthodes permettant de traiter un cancer, des compositions permettant de traiter un cancer, et des méthodes et des compositions permettant de diagnostiquer et/ou de détecter un cancer. Plus particulièrement, cette invention concerne des compositions et des méthodes permettant de traiter, de diagnostiquer et de détecter des cancers associés à une surexpression de FZDIO.
PCT/US2007/084293 2006-11-14 2007-11-09 Méthodes permettant de traiter, de diagnostiquer ou de détecter un cancer WO2008061020A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP07871425A EP2084540A2 (fr) 2006-11-14 2007-11-09 Methodes permettant de traiter, de diagnostiquer ou de detecter un cancer
MX2009005058A MX2009005058A (es) 2006-11-14 2007-11-09 Metodos para tratar, diagnosticar o detectar cancer.
CA002668714A CA2668714A1 (fr) 2006-11-14 2007-11-09 Methodes permettant de traiter, de diagnostiquer ou de detecter un cancer
JP2009536514A JP2010509368A (ja) 2006-11-14 2007-11-09 がんを処置、診断または検出する方法
BRPI0718850-1A2A BRPI0718850A2 (pt) 2006-11-14 2007-11-09 Métodos de tratar, diagnosticar ou detectar câncer
AU2007319360A AU2007319360A1 (en) 2006-11-14 2007-11-09 Methods of treating, diagnosing or detecting cancer

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US85888206P 2006-11-14 2006-11-14
US60/858,882 2006-11-14

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WO2008061020A2 true WO2008061020A2 (fr) 2008-05-22
WO2008061020A3 WO2008061020A3 (fr) 2008-08-07
WO2008061020A9 WO2008061020A9 (fr) 2008-11-13

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EP (1) EP2084540A2 (fr)
JP (1) JP2010509368A (fr)
KR (1) KR20090080082A (fr)
CN (1) CN101558308A (fr)
AU (1) AU2007319360A1 (fr)
BR (1) BRPI0718850A2 (fr)
CA (1) CA2668714A1 (fr)
MX (1) MX2009005058A (fr)
WO (1) WO2008061020A2 (fr)

Cited By (11)

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Publication number Priority date Publication date Assignee Title
US7723477B2 (en) 2005-10-31 2010-05-25 Oncomed Pharmaceuticals, Inc. Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth
US7982013B2 (en) 2008-09-26 2011-07-19 Oncomed Pharmaceuticals, Inc. Frizzled-binding agents and uses thereof
WO2012135845A1 (fr) 2011-04-01 2012-10-04 Qiagen SIGNATURE D'EXPRESSION GÉNIQUE POUR LA VOIE DE SIGNALISATION Wnt/CATÉNINE β ET UTILISATION DE CELLE-CI
WO2013025446A2 (fr) * 2011-08-12 2013-02-21 Omeros Corporation Anticorps monoclonaux anti-fzd10 et leurs procédés d'utilisation
US8551789B2 (en) 2010-04-01 2013-10-08 OncoMed Pharmaceuticals Frizzled-binding agents and their use in screening for WNT inhibitors
US9157904B2 (en) 2010-01-12 2015-10-13 Oncomed Pharmaceuticals, Inc. Wnt antagonists and methods of treatment and screening
US9168300B2 (en) 2013-03-14 2015-10-27 Oncomed Pharmaceuticals, Inc. MET-binding agents and uses thereof
CN105264381A (zh) * 2013-05-16 2016-01-20 国立大学法人京都大学 用于确定癌症预后的方法
US9266959B2 (en) 2012-10-23 2016-02-23 Oncomed Pharmaceuticals, Inc. Methods of treating neuroendocrine tumors using frizzled-binding agents
US9359444B2 (en) 2013-02-04 2016-06-07 Oncomed Pharmaceuticals Inc. Methods and monitoring of treatment with a Wnt pathway inhibitor
US9850311B2 (en) 2005-10-31 2017-12-26 Oncomed Pharmaceuticals, Inc. Compositions and methods for diagnosing and treating cancer

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013157410A1 (fr) * 2012-04-17 2013-10-24 Hoya株式会社 Peptide de liaison de fzd10
CN103048446B (zh) * 2012-12-25 2015-02-04 苏州浩欧博生物医药有限公司 一种促黄体生成激素的纳米磁微粒化学发光测定试剂盒及其制备方法和检测方法

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KR20090080082A (ko) 2009-07-23
JP2010509368A (ja) 2010-03-25
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EP2084540A2 (fr) 2009-08-05
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