US 2004/0018528 A1Published application

Novel biomarkers of tyrosine kinase inhibitor exposure and activity in mammals

AssigneeSugen, Inc.

InventorsAlyssa Morimoto, Samuel DePrimo, Anne-Marie O'Farrell, Beverly D. Smolich, William C. Manning, Sarah A. Walter, James W. Schilling JR., Julie Cherrington

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Abstract

The present invention describes novel methods that measure in a mammal the level of at least one biomarker, such as a protein and/or mRNA transcript. Based on the level of at least one biomarker in a mammal exposed to a test compound, compared to the level of the biomarker(s) in a mammal that has not been exposed to a test compound, the ability of the test compound to inhibit tyrosine kinase activity can be determined. The invention also relates to novel methods, wherein a change in the level of at least one biomarker in a mammal exposed to a compound, compared to the level of the biomarker(s) in a mammal that has not been exposed to the compound, indicates whether the mammal is being exposed to, or is experiencing or will experience a therapeutic or toxic effect in response to, a compound that inhibit tyrosine kinase activity.

Claims30

Dependent claims

A method for determining whether a test compound inhibits tyrosine kinase activity in a mammal, comprising:

(a) measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
(b), exposing the mammal to the test compound;
and
(c) following the exposing of step (b), measuring in the mammal the level of at least one of the proteins and/or mRNA transcripts measured in step (a),
wherein a difference in the level of said protein and/or mRNA transcript measured in (c), compared to the level of protein and/or mRNA transcript measured in step (a) indicates that the test compound is an inhibitor of tyrosine kinase in the mammal.

5 more elements

A method for determining whether a test compound inhibits tyrosine kinase activity in a mammal, comprising:

(a) exposing the mammal to the test compound;
and
(b) following the exposing of step (a), measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1,
wherein a difference in the level of said protein and/or mRNA measured in (b), compared to the level of protein and/or mRNA in a mammal that has not been exposed to said test compound, indicates that the compound is an inhibitor of tyrosine kinase in the mammal.

4 more elements

A method for determining whether a mammal has been exposed to a test compound that inhibits tyrosine kinase activity, comprising:

(a) measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
(b), exposing the mammal to the test compound;
and
(c) following the exposing of step (b), measuring in the mammal the level of at least one of the proteins and/or mRNA transcripts measured in step (a),
wherein a difference in the level of said protein and/or mRNA measured in (c), compared to the level of protein and/or mRNA in step (a) indicates that the mammal has been exposed to a test compound that inhibits tyrosine kinase activity.

5 more elements

A method for determining whether a mammal has been exposed to a test compound that inhibits tyrosine kinase activity, comprising

(a) exposing the mammal to the test compound;
and
(b) following the exposing of step (a), measuring in a mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1,
wherein a difference in the level of said protein and/or mRNA measured in (b), compared to the level of protein and/or mRNA in a mammal that has not been exposed to said test compound, indicates that the mammal has been exposed to a test compound that is an inhibitor of tyrosine kinase.

4 more elements

A method for determining whether a mammal is responding to a compound that inhibits tyrosine kinase activity, comprising:

(a) measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
(b), exposing the mammal to the compound;
and
(c) following the exposing of step (b), measuring in the mammal the level of at least one of the proteins and/or mRNA transcripts measured in step (a),
wherein a difference in the level of said protein and/or mRNA transcripts measured in (c), compared to the level of protein and/or mRNA transcript for said protein in step (a) indicates that that the mammal is responding to the compound that inhibits tyrosine kinase activity.

5 more elements

A method for determining whether a mammal is responding to a compound that inhibits tyrosine kinase activity, comprising:

(a) exposing the mammal to the compound;
and
(b) following the exposing step (a), measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1,
wherein a difference in the level of said protein and/or mRNA measured in (b), compared to the level of protein and/or mRNA in a mammal that has not been exposed to said compound, indicates that the mammal is responding to the compound that inhibits tyrosine kinase.

4 more elements

A method for identifying a mammal that will respond therapeutically to a method of treating cancer comprising administering at least one inhibitor of a VEGFR and/or PDGFR tyrosine kinase, wherein the method for identifying the mammal comprises:

(a) measuring in the mammal the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
(b) exposing the mammal to at least one inhibitor of a VEGFR and/or PDGFR tyrosine kinase;
and
(c) following the exposing of step (b), measuring in the mammal the level of at least one of the proteins and/or mRNA transcripts measured in step (a),
wherein a difference in the level of said protein and/or mRNA transcripts measured in (c), compared to the level of protein and/or mRNA transcript for said protein in step (a) indicates that that the mammal will respond therapeutically to a method of treating cancer comprising administering at least one inhibitor of a VEGFR and/or PDGFR tyrosine kinase.

5 more elements

A method for testing or predicting whether a mammal will respond therapeutically to a method of treating cancer comprising administering at least one inhibitor of a VEGFR and/or PDGFR tyrosine kinase, wherein the method for testing or predicting comprises:

(a) measuring in a mammal with cancer the level of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
(b) measuring in the same type of mammal without cancer, the level of at least one of the same proteins and/or mRNA transcripts measured in step (a);
(c) comparing levels of said proteins and/or mRNA transcripts measured in (a) and (b);
wherein a difference in the level of said protein and/or mRNA in the mammal with cancer as measured in step (a), compared to the level of said protein and/or mRNA in the mammal without cancer as measured in step (b), indicates that the mammal will respond therapeutically to at least one inhibitor of a VEGFR and/or PDGFR tyrosine kinase.

4 more elements

A kit comprising:

(a) antibody and/or nucleic acid for detecting the presence of at least one of the following proteins and/or mRNA transcripts for such proteins and/or genes:
PAI-1, TIMP-1, vinculin, VEGF, PLGF, VEGF/PLGF heterodimers, MIG, IP-10, I-TAC, eucaryotic initiation factor 4A11, human (clone 5) orphan G protein-coupled receptor (Genbank Accession No. L06797;
CXCR4), Homo sapiens thymosin beta-10 gene, Homo sapiens hnRNPcore protein A1, human leucocyte antigen (CD37), human MHC class II HLA-DR beta-1, Homo sapiens translation initiation factor elF3 p66 subunit, Homo sapiens nm23-H2 gene, human acidic ribosomal phosphoprotein P0, human cyclophilin, GenBank Accession No. AI541256 (Homo sapiens cDNA), human T-cell receptor active beta chain, human MHC class II lymphocyte antigen (HLA-DP) beta chain, Homo sapiens MAP kinase kinase 3 (MKK3), human RLIP76 protein, MMP-9, lactoferrin, lipocalin-2, CD24 antigen, basic transcription factor 3 homologue, c-jun proto-oncogene, c-fos cellular oncogene, tyrosine phosphatase non-receptor type 2, cdc2 related protein kinase, cyclin C, DNA polymerase gamma, protein kinase C alpha, lipocortin II/annexin A2, histone H2B member R, amphiregulin, basic transcription factor 3, phosphoinositol 3-kinase p110 subunit, GCP-2, IL-1α, IL-1β, IL-2, NT4, GCP-2, IGFBP-1, GRO-β, TNFR1, FLT3L, IL-6, IL-8, C-reactive protein, MCP-1, TNFα, TARC, MMP7, leptin, pro-MMP1 (interstitial collegenase precursor), ITIH4, soluble VEGF receptor 2 (sVEGFR2), human KIAA0195, human beta-tubulin class III isotype (beta-3), human tropomyosin, 1-phosphatidyl inositol-4-phosphate-5-kinase isoform C;
human MLC emb gene for embryonic myosin alkaline light chain, Homo sapiens glyoxalase II, Homo sapiens trans-golgi network glycoprotein 48, histone H2B, Genbank Accession No. W26677 (Homo sapiens cDNA), human PMI gene for a putative receptor protein, human DNA-binding protein A (dbpA), ephrin receptor EphB4, hanukah factor/granzyme A, von Hippel-Lindau (VHL) tumor suppressor, OB-cadherin 1, OB-cadherin 2, phosphoinositol 3-phosphate-binding protein-3 (PEPP3), phosphoinositol 3-kinase p85 subunit, mucin 1, hepatitis C-associated microtubular aggregate p44, ErbB3/HER3 receptor tyrosine kinase, gelsolin, cyclin D2, ENA-78 and MPIF-1;
and
(b) instructions for determining whether or not a mammal will respond therapeutically to a method of treating cancer comprising administering a compound that inhibits tyrosine kinase activity.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/440,464Filed 19 May 2003
Priority: 17 May 2002
Published: 29 Jan 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification2 codes

C12Q 1/485
Involving transferase: involving kinase
C12Q
Measuring or testing processes involving enzymes, nucleic acids or microorganisms

Family

Application60/380,872Us provisional application · filed 17 May 2002
Application60/448,922Us provisional application · filed 24 Feb 2003
Application60/448,874Us provisional application · filed 24 Feb 2003
US 2004/0018528 A1This patent

From the US filing history. Foreign family members aren’t listed.

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