Biomarkers for predicting anti-tnf responsiveness or non-responsiveness
AssigneesBiogen Idec MA Inc., The Feinstein Institute for Medical Research
InventorsJohn P. Carulli, Peter K. Gregersen, Franak Batliwalla, Jadwiga Bienkowska, Chunyu Liu
Life of this patent
Estimating the term…
Abstract
The present disclosure provides biomarkers that are predictive a subject's responsiveness or non-responsiveness to an anti-TNF therapy. The biomarkers, compositions, and methods described herein are useful in selecting appropriate treatment modalities (e.g., an anti-TNF therapy or a non-anti-TNF therapy) for a subject suffering from a disease such as an immune disorder.
Claims42
A method of predicting the response of a subject to a therapy comprising an anti-TNF agent, the method comprising:
- providing a biological sample obtained from a subject that has an immune disorder;
- and
- measuring the expression level of one or more genes in the biological sample, wherein the one or more genes comprise at least one gene selected from the group consisting of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, ZFP36L1, ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, and SFRS2,
- wherein at least one of (i) an elevated expression level, as compared to a healthy individual, of one or more of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, or ZFP36L1, or (ii) a reduced expression level, as compared to a healthy individual, of one or more of ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, or SFRS2 predicts that the subject will respond to a therapy comprising an anti-TNF agent.
A method of predicting the response of a subject to a therapy comprising an anti-TNF agent, the method comprising:
- providing a biological sample obtained from a subject that has an immune disorder;
- and
- measuring the expression level of one or more genes in the biological sample, wherein the one or more genes comprise at least one gene selected from the group consisting of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, ZFP36L1, ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, and SFRS2,
- wherein at least one of (i) an elevated expression level, as compared to a healthy individual, of one or more of ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, or SFRS2, or (ii) a reduced expression level, as compared to a healthy individual, of one or more of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, or ZFP36L1 predicts that the subject will not respond to a therapy comprising an anti-TNF agent.
A method of treating an immune disorder, the method comprising administering to a subject in need thereof an effective amount of a therapy comprising an anti-TNF agent, wherein the subject has been identified as having at least one of (i) an elevated expression level, as compared to a healthy individual, of one or more of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, or ZFP36L1, or (ii) a reduced expression level, as compared to a healthy individual, of one or more of ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, or SFRS2.
A method of predicting the response of a subject to a therapy comprising an anti-TNF agent, the method comprising:
- providing a biological sample obtained from a subject that has an immune disorder;
- and
- detecting the presence or absence of one or more SNP genotypes in the biological sample, wherein the one or more SNP genotypes comprise at least one SNP genotype selected from the group consisting of rsl 1778767 (A/A), rs11780500 (A/A), rs11780500 (G/G), rs1422422 (A/A), rs1441209 (A/A), rs1968201 (A/A), rs2028446 (A/A), rs2028446 (A/G), rs2028446 (G/G), rs2170331 (A/G), rs2170331 (G/G), rs2814707 (A/G), rs2814707 (G/G), rs3019293 (A/A), rs3087615 (A/C), rs3087615 (C/C), rs3849942 (A/G), rs3849942 (G/G), rs437943 (A/A), rs4562286 (A/A), rs4976592 (A/A), rs6531358 (A/A), rs6665006 (A/A), rs6665006 (A/G), rs7046653 (A/G), rs7046653 (G/G), rs774359 (A/A), rs868856 (A/G), and rs868856 (G/G),
- wherein the presence of one or more of rs11778767 (A/A), rs11780500 (A/A), rs11780500 (G/G), rs1422422 (A/A), rs1441209 (A/A), rs1968201 (A/A), rs2028446 (A/A), rs2028446 (A/G), rs2028446 (G/G), rs2170331 (A/G), rs2170331 (G/G), rs2814707 (A/G), rs2814707 (G/G), rs3019293 (A/A), rs3087615 (A/C), rs3087615 (C/C), rs3849942 (A/G), rs3849942 (G/G), rs437943 (A/A), rs4562286 (A/A), rs4976592 (A/A), rs6531358 (A/A), rs6665006 (A/A), rs6665006 (A/G), rs7046653 (A/G), rs7046653 (G/G), rs774359 (A/A), rs868856 (A/G), or rs868856 (G/G) predicts that the subject will respond to a therapy comprising an anti-TNF agent.
A method of predicting the response of a subject to a therapy comprising an anti-TNF agent, the method comprising:
- providing a biological sample obtained from a subject that has an immune disorder;
- and
- detecting the presence or absence of one or more SNP genotypes in the biological sample, wherein the one or more SNP genotypes comprise at least one SNP genotype selected from the group consisting of rs11778767 (A/G), rs11778767 (G/G), rs11780500 (A/G), rs1422422 (A/G), rs1422422 (G/G), rs1441209 (A/G), rs1441209 (G/G), rs1968201 (A/G), rs2170331 (A/A), rs2814707 (A/A), rs3019293 (A/G), rs3019293 (G/G), rs3849942 (A/A), rs437943 (A/G), rs437943 (G/G), rs4562286 (A/G), rs4562286 (G/G), rs4976592 (A/G), rs4976592 (G/G), rs6531358 (A/G), rs6531358 (G/G), rs6665006 (G/G), rs7046653 (A/A), rs774359 (A/G), rs774359 (G/G), rs868856 (A/A), rs983332 (A/C), rs928655 (A/G), rs13393173 (A/G), rs437943 (A/G), rs10945919 (A/G), rs854555 (A/C), rs854548 (A/G), rs854547 (A/G), rs7046653 (A/G), rs868856 (C/T), rs774359 (C/T), rs2814707 (A/G), rs3849942 (A/G), rs6028945 (G/T), rs6138150 (C/T), rs6071980 (C/T), rs1800896 (A/G), rs3024490 (A/C), rs231726 (A/G), rs3096851 (A/C), rs6708660 (A/G), rs2523619 (A/G), rs3915971 (A/G), rs9264869 (A/G), rs2239804 (A/G), rs2395175 (A/G), rs2395185 (A/C), rs2516049 (A/G), rs660895 (A/G), rs7026551 (A/C), rs4803455 (A/C), rs983332 (A/A), rs928655 (A/A), rs13393173 (A/A), rs437943 (G/G), rs10945919 (G/G), rs854555 (A/A), rs854548 (A/A), rs7046653 (A/A), rs868856 (T/T), rs774359 (C/C), rs2814707 (A/A), rs3849942 (A/A), rs6028945 (T/T), rs6138150 (T/T), rs6071980 (C/C), rs1800896 (A/A), rs3024490 (A/A), rs231726 (A/A), rs3096851 (C/C), rs6708660 (A/A), rs2523619 (G/G), rs3915971 (A/A), rs9264869 (A/A), rs2239804 (A/A), rs2395175 (G/G), rs2395185 (C/C), rs2516049 (A/A), rs660895 (A/A), rs7026551 (C/C), rs4803455 (C/C), and any of the SNP genotypes depicted in Table 13,
- wherein the presence of one or more of rs11778767 (A/G), rs11778767 (G/G), rs11780500 (A/G), rs1422422 (A/G), rs1422422 (G/G), rs1441209 (A/G), rs1441209 (G/G), rs1968201 (A/G), rs2170331 (A/A), rs2814707 (A/A), rs3019293 (A/G), rs3019293 (G/G), rs3849942 (A/A), rs437943 (A/G), rs437943 (G/G), rs4562286 (A/G), rs4562286 (G/G), rs4976592 (A/G), rs4976592 (G/G), rs6531358 (A/G), rs6531358 (G/G), rs6665006 (G/G), rs7046653 (A/A), rs774359 (A/G), rs774359 (G/G), rs868856 (A/A), rs983332 (A/C), rs928655 (A/G), rs13393173 (A/G), rs437943 (A/G), rs10945919 (A/G), rs854555 (A/C), rs854548 (A/G), rs854547 (A/G), rs7046653 (A/G), rs868856 (C/T), rs774359 (C/T), rs2814707 (A/G), rs3849942 (A/G), rs6028945 (G/T), rs6138150 (C/T), rs6071980 (C/T), rs1800896 (A/G), rs3024490 (A/C), rs231726 (A/G), rs3096851 (A/C), rs6708660 (A/G), rs2523619 (A/G), rs3915971 (A/G), rs9264869 (A/G), rs2239804 (A/G), rs2395175 (A/G), rs2395185 (A/C), rs2516049 (A/G), rs660895 (A/G), rs7026551 (A/C), rs4803455 (A/C), rs983332 (A/A), rs928655 (A/A), rs13393173 (A/A), rs437943 (G/G), rs10945919 (G/G), rs854555 (A/A), rs854548 (A/A), rs7046653 (A/A), rs868856 (T/T), rs774359 (C/C), rs2814707 (A/A), rs3849942 (A/A), rs6028945 (T/T), rs6138150 (T/T), rs6071980 (C/C), rs1800896 (A/A), rs3024490 (A/A), rs231726 (A/A), rs3096851 (C/C), rs6708660 (A/A), rs2523619 (G/G), rs3915971 (A/A), rs9264869 (A/A), rs2239804 (A/A), rs2395175 (G/G), rs2395185 (C/C), rs2516049 (A/A), rs660895 (A/A), rs7026551 (C/C), rs4803455 (C/C), or any of the SNP genotypes depicted in Table 13 predicts that the subject will not respond to a therapy comprising an anti-TNF agent.
A method of treating an immune disorder, the method comprising administering to a subject in need thereof an effective amount of a therapy comprising an anti-TNF agent, wherein the subject has been identified as having one or more single nucleotide polymorphisms (SNPs) genotypes selected from the group consisting of rs11778767 (A/A), rs11780500 (A/A), rs11780500 (G/G), rs1422422 (A/A), rs1441209 (A/A), rs1968201 (A/A), rs2028446 (A/A), rs2028446 (A/G), rs2028446 (G/G), rs2170331 (A/G), rs2170331 (G/G), rs2814707 (A/G), rs2814707 (G/G), rs3019293 (A/A), rs3087615 (A/C), rs3087615 (C/C), rs3849942 (A/G), rs3849942 (G/G), rs437943 (A/A), rs4562286 (A/A), rs4976592 (A/A), rs6531358 (A/A), rs6665006 (A/A), rs6665006 (A/G), rs7046653 (A/G), rs7046653 (G/G), rs774359 (A/A), rs868856 (A/G), and rs868856 (G/G).
A composition comprising at least five polynucleotides that selectively hybridize to each of at least five genes selected from the group consisting of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, ZFP36L1, ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, and SFRS2.
A composition comprising at least five polynucleotides that selectively hybridize to each of at least five SNP genotypes selected from the group consisting of rs11778767 (A/A), rs11780500 (A/A), rs11780500 (G/G), rs1422422 (A/A), rs1441209 (A/A), rs1968201 (A/A), rs2028446 (A/A), rs2028446 (A/G), rs2028446 (G/G), rs2170331 (A/G), rs2170331 (G/G), rs2814707 (A/G), rs2814707 (G/G), rs3019293 (A/A), rs3087615 (A/C), rs3087615 (C/C), rs3849942 (A/G), rs3849942 (G/G), rs437943 (A/A), rs4562286 (A/A), rs4976592 (A/A), rs6531358 (A/A), rs6665006 (A/A), rs6665006 (A/G), rs7046653 (A/G), rs7046653 (G/G), rs774359 (A/A), rs868856 (A/G), rs868856 (G/G), rs11778767 (A/G), rs11778767 (G/G), rs11780500 (A/G), rs1422422 (A/G), rs1422422 (G/G), rs1441209 (A/G), rs1441209 (G/G), rs1968201 (A/G), rs2170331 (A/A), rs2814707 (A/A), rs3019293 (A/G), rs3019293 (G/G), rs3849942 (A/A), rs437943 (A/G), rs437943 (G/G), rs4562286 (A/G), rs4562286 (G/G), rs4976592 (A/G), rs4976592 (G/G), rs6531358 (A/G), rs6531358 (G/G), rs6665006 (G/G), rs7046653 (A/A), rs774359 (A/G), rs774359 (G/G), rs868856 (A/A), rs983332 (A/C), rs928655 (A/G), rs13393173 (A/G), rs437943 (A/G), rs10945919 (A/G), rs854555 (A/C), rs854548 (A/G), rs854547 (A/G), rs7046653 (A/G), rs868856 (C/T), rs774359 (C/T), rs2814707 (A/G), rs3849942 (A/G), rs6028945 (G/T), rs6138150 (C/T), rs6071980 (C/T), rs1800896 (A/G), rs3024490 (A/C), rs231726 (A/G), rs3096851 (A/C), rs6708660 (A/G), rs2523619 (A/G), rs3915971 (A/G), rs9264869 (A/G), rs2239804 (A/G), rs2395175 (A/G), rs2395185 (A/C), rs2516049 (A/G), rs660895 (A/G), rs7026551 (A/C), rs4803455 (A/C), rs983332 (A/A), rs928655 (A/A), rs13393173 (A/A), rs437943 (G/G), rs10945919 (G/G), rs854555 (A/A), rs854548 (A/A), rs7046653 (A/A), rs868856 (T/T), rs774359 (C/C), rs2814707 (A/A), rs3849942 (A/A), rs6028945 (T/T), rs6138150 (T/T), rs6071980 (C/C), rs1800896 (A/A), rs3024490 (A/A), rs231726 (A/A), rs3096851 (C/C), rs6708660 (A/A), rs2523619 (G/G), rs3915971 (A/A), rs9264869 (A/A), rs2239804 (A/A), rs2395175 (G/G), rs2395185 (C/C), rs2516049 (A/A), rs660895 (A/A), rs7026551 (C/C), rs4803455 (C/C), and any of the SNP genotypes depicted in Table 13.
A kit comprising:
- an array comprising a plurality of polynucleotides bound to a solid support, wherein the plurality comprises at least five polynucleotides that selectively hybridize to each of at least five genes selected from the group consisting of ANKIB1, ARF1, ARF5, BRWD2, CALM2, CLTB, COL4A3BP, C9orf80, EGLN2, HDAC5, LGALS9, MYLIP, PCBP2, PGK1, RBBP4, RER1, RPA3, SERF2, SLC25A39, SRGAP2, TUG1, YIPF6, ZNF294, ZFP36L1, ANKRD12, CAMK2G-, CASP5, CXorf52, DNAH1, EEA1, FAM44A, FOXJ3, HDAC4, MNT, MXRA7, PTCH1, SEL1L, and SFRS2;
- and
- instructions for detecting the presence or amount of one of more of the polynucleotides in a sample.
A kit comprising:
- an array comprising a plurality of polynucleotides bound to a solid support, wherein the plurality comprises at least five polynucleotides that selectively hybridize to each of at least five SNP genotypes selected from the group consisting of rs11778767 (A/A), rs11780500 (A/A), rs11780500 (G/G), rs1422422 (A/A), rs1441209 (A/A), rs1968201 (A/A), rs2028446 (A/A), rs2028446 (A/G), rs2028446 (G/G), rs2170331 (A/G), rs2170331 (G/G), rs2814707 (A/G), rs2814707 (G/G), rs3019293 (A/A), rs3087615 (A/C), rs3087615 (C/C), rs3849942 (A/G), rs3849942 (G/G), rs437943 (A/A), rs4562286 (A/A), rs4976592 (A/A), rs6531358 (A/A), rs6665006 (A/A), rs6665006 (A/G), rs7046653 (A/G), rs7046653 (G/G), rs774359 (A/A), rs868856 (A/G), rs868856 (G/G), rs11778767 (A/G), rs11778767 (G/G), rs11780500 (A/G), rs1422422 (A/G), rs1422422 (G/G), rs1441209 (A/G), rs1441209 (G/G), rs1968201 (A/G), rs2170331 (A/A), rs2814707 (A/A), rs3019293 (A/G), rs3019293 (G/G), rs3849942 (A/A), rs437943 (A/G), rs437943 (G/G), rs4562286 (A/G), rs4562286 (G/G), rs4976592 (A/G), rs4976592 (G/G), rs6531358 (A/G), rs6531358 (G/G), rs6665006 (G/G), rs7046653 (A/A), rs774359 (A/G), rs774359 (G/G), rs868856 (A/A), rs983332 (A/C), rs928655 (A/G), rs13393173 (A/G), rs437943 (A/G), rs10945919 (A/G), rs854555 (A/C), rs854548 (A/G), rs854547 (A/G), rs7046653 (A/G), rs868856 (C/T), rs774359 (C/T), rs2814707 (A/G), rs3849942 (A/G), rs6028945 (G/T), rs6138150 (C/T), rs6071980 (C/T), rs1800896 (A/G), rs3024490 (A/C), rs231726 (A/G), rs3096851 (A/C), rs6708660 (A/G), rs2523619 (A/G), rs3915971 (A/G), rs9264869 (A/G), rs2239804 (A/G), rs2395175 (A/G), rs2395185 (A/C), rs2516049 (A/G), rs660895 (A/G), rs7026551 (A/C), rs4803455 (A/C), rs983332 (A/A), rs928655 (A/A), rs13393173 (A/A), rs437943 (G/G), rs10945919 (G/G), rs854555 (A/A), rs854548 (A/A), rs7046653 (A/A), rs868856 (T/T), rs774359 (C/C), rs2814707 (A/A), rs3849942 (A/A), rs6028945 (T/T), rs6138150 (T/T), rs6071980 (C/C), rsl 800896 (A/A), rs3024490 (A/A), rs231726 (A/A), rs3096851 (C/C), rs6708660 (A/A), rs2523619 (G/G), rs3915971 (A/A), rs9264869 (A/A), rs2239804 (A/A), rs2395175 (G/G), rs2395185 (C/C), rs2516049 (A/A), rs660895 (A/A), rs7026551 (C/C), rs4803455 (C/C), and any of the SNP genotypes depicted in Table 13;
- and
- instructions for detecting the presence or amount of one of more of the SNP genotypes in a sample.
Dependencies are inferred from the claim text.