# US 2010/0167268 A1 · Seroconversion assays for detecting xenotropic murine leukemia virus-related virus > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0167268 A1 - Document ID: US20100167268A1 - Status: Published application - Kind: A1 - Application number: 12/575,467 - Filed: 2009-10-07 - Published: 2010-07-01 - Earliest claimed: 2009-07-15 - Inventors: Judy A. Mikovits; Francis W. Ruscetti; Sandra K. Ruscetti - Web page: https://patentgrep.com/patent/US20100167268A1 ## CPC - G01N 33/56983: {Viruses} - G01N 2333/15: Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus - G01N 2469/20: Detection of antibodies in sample from host which are directed against antigens from microorganisms - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Methods of detecting, diagnosing, monitoring or managing an XMRV-related disease such as an XMRV-related neuroimmune disease such as chronic fatigue syndrome or an XMRV-related lymphoma such as mantle cell lymphoma in a subject are disclosed. These methods comprise determining presence, absence or quantity of antibodies against XMRV in a sample from a subject. ## Claims ### Claim 1 A method of detecting presence, absence or quantity of antibody against XMRV in a subject, the method comprising: providing a biological sample comprising antibody from the subject; forming a mixture comprising a) at least one gammaretrovirus antigen, b) the sample, and c) a competitive probe against the at least one Gammaretrovirus antigen, under conditions sufficient for formation of a complex comprising the at least one Gammaretrovirus antigen and the competitive probe; and detecting quantity of a complex comprising the at least one Gammaretrovirus antigen and the competitive probe, whereby if the sample comprises antibody against the Gammaretrovirus antigen, the quantity of complex is less than that of a complex formed from a mixture comprising a) the at least one Gammaretrovirus antigen, b) a control sample not comprising antibody against the at least one Gammaretrovirus antigen, and c) the competitive probe against the at least one Gammaretrovirus antigen. ### Claim 2 (depends on 1) A method in accordance with claim 1, wherein the at least one Gammaretrovirus antigen is other than an XMRV gag polypeptide. ### Claim 3 (depends on 2) A method in accordance with claim 2, wherein the XMRV gag polypeptide is selected from the group consisting of a p10 polypeptide, a p15 polypeptide and a p30 polypeptide. ### Claim 4 (depends on 3) A method in accordance with claim 3, wherein the XMRV gag polypeptide is a p30 polypeptide. ### Claim 5 (depends on 1) A method in accordance with claim 1, wherein the method is other than a double antigen sandwich assay. ### Claim 6 (depends on 1) A method in accordance with claim 1, wherein the subject is a human. ### Claim 7 (depends on 1) A method in accordance with claim 1, wherein the subject is a person having, suspected of having, or at risk for developing an XMRV-related disease. ### Claim 8 (depends on 7) A method in accordance with claim 7, wherein the XMRV-related disease is an XMRV-related prostate cancer. ### Claim 9 (depends on 7) A method in accordance with claim 7, wherein the XMRV-related disease is an XMRV-related lymphoma. ### Claim 10 (depends on 9) A method in accordance with claim 9, wherein the XMRV-related lymphoma is selected from the group consisting of an XMRV-related Mantle Cell Lymphoma (MCL) and an XMRV-related Chronic Lymphocytic Leukemia lymphoma (CLL). ### Claim 11 (depends on 6) A method in accordance with claim 6, wherein the XMRV-related disease is an XMRV-related neuroimmune disease. ### Claim 12 (depends on 11) A method in accordance with claim 11, wherein the XMRV-related neuroimmune disease is selected from the group consisting of chronic fatigue syndrome (CFS), Niemann-Pick Type C Disease, fibromyalgia, Multiple Sclerosis (MS), Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS) and autism. ### Claim 13 (depends on 11) A method in accordance with claim 11, wherein the XMRV-related neuroimmune disease is chronic fatigue syndrome (CFS). ### Claim 14 (depends on 12) A method in accordance with claim 12, wherein the Multiple Sclerosis is Atypical Multiple Sclerosis. ### Claim 15 (depends on 6) A method in accordance with claim 6, wherein the subject exhibits signs and/or symptoms of a neuroimmune disease and/or a lymphoma. ### Claim 16 (depends on 1) A method in accordance with claim 1, wherein the sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, a sputum sample and a cerebrospinal fluid sample. ### Claim 17 (depends on 1) A method in accordance with claim 1, wherein the sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample and a cerebrospinal fluid sample. ### Claim 18 (depends on 1) A method in accordance with claim 1, wherein the sample is selected from the group consisting of a blood sample, a serum sample and a plasma sample. ### Claim 19 (depends on 18) A method in accordance with claim 18, wherein the sample is a plasma sample. ### Claim 20 (depends on 18) A method in accordance with claim 18, wherein the blood sample is a peripheral blood sample. ### Claim 21 (depends on 1) A method in accordance with claim 1, wherein the at least one Gammaretrovirus antigen comprises a contiguous sequence of at least 4 amino acids of an XMRV polypeptide. ### Claim 22 (depends on 1) A method in accordance with claim 1, wherein the at least one Gammaretrovirus antigen is comprised by at least one cell ex vivo. ### Claim 23 (depends on 22) A method in accordance with claim 22, wherein the at least one cell ex vivo is a mammalian cell expressing at least one Gammaretrovirus antigen ex vivo. ### Claim 24 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having at least 95% sequence identity with an SFFV Env protein. ### Claim 25 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having at least 96% sequence identity with an SFFV Env protein. ### Claim 26 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having at least 97% sequence identity with an SFFV Env protein. ### Claim 27 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having at least 98% sequence identity with an SFFV Env protein. ### Claim 28 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having at least 99% sequence identity with an SFFV Env protein. ### Claim 29 (depends on 22) A method in accordance with claim 22, wherein the at least one Gammaretrovirus antigen is a polypeptide having 100% sequence identity with an SFFV Env protein. ### Claim 30 (depends on 23) A method in accordance with claim 23, wherein the mammalian cell is a BaF3ER cell. ### Claim 31 (depends on 23) A method in accordance with claim 23, wherein the mammalian cell expressing at least one Gammaretrovirus antigen is a BaF3ER-SFFVEnV cell expressing SFFV Env protein. ### Claim 32 (depends on 1) A method in accordance with claim 1, wherein the at least one Gammaretrovirus antigen is an SFFV antigen. ### Claim 33 (depends on 32) A method in accordance with claim 32, wherein the SFFV antigen is an SFFV Env antigen. ### Claim 34 (depends on 1) A method in accordance with claim 1, wherein the detecting presence, absence or quantity of a complex comprising the at least one Gammaretrovirus antigen and antibody against the at least one Gammaretrovirus antigen comprises contacting the mixture with at least one primary probe directed against antibody from the subject. ### Claim 35 (depends on 34) A method in accordance with claim 34, wherein the at least one primary probe is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, an aptamer, and an avimer. ### Claim 36 (depends on 34) A method in accordance with claim 34, wherein the at least one primary probe is an antibody or an antigen-binding fragment thereof. ### Claim 37 (depends on 36) A method in accordance with claim 36, wherein the antibody is a polyclonal antibody or a monoclonal antibody. ### Claim 38 (depends on 36) A method in accordance with claim 36, wherein the antigen-binding fragment is an Fab fragment. ### Claim 39 (depends on 1) A method in accordance with claim 1, wherein the competitive probe is an antibody against a gammaretrovirus antigen. ### Claim 40 (depends on 39) A method in accordance with claim 39, wherein the antibody against a gammaretrovirus antigen is a polyclonal antibody. ### Claim 41 (depends on 39) A method in accordance with claim 39, wherein the antibody against a gammaretrovirus antigen is a monoclonal antibody. ### Claim 42 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a murine leukemia-related retrovirus. ### Claim 43 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a Xenotropic murine leukemia virus. ### Claim 44 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a nonecotropic murine leukemia virus. ### Claim 45 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a polytropic murine leukemia virus (Mmpv). ### Claim 46 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a modified polytropic murine leukemia virus. ### Claim 47 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against an XMRV. ### Claim 48 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against an SFFV. ### Claim 49 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is selected from the group consisting of an antibody against a gammaretrovirus gag protein, an antibody against a gammaretrovirus env protein and an antibody against a gammaretrovirus pol protein. ### Claim 50 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is selected from the group consisting of an antibody against a gammaretrovirus env protein and an antibody against a gammaretrovirus pol protein. ### Claim 51 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an antibody against a gammaretrovirus env protein. ### Claim 52 (depends on 34) A method in accordance with claim 34, wherein the antibody against a gammaretrovirus antigen is an anti gp 55 Env antibody. ### Claim 53 (depends on 51) A method in accordance with claim 51, wherein the antibody against a gammaretrovirus antigen is monoclonal antibody MAb 7C10. ### Claim 54 (depends on 36) A method in accordance with claim 36, wherein the antibody is a polyclonal antibody against at least one Gammaretrovirus antigen. ### Claim 55 (depends on 36) A method in accordance with claim 36, wherein the detecting comprises an assay selected from the group consisting of an immunoprecipitation assay, an ELISA, a radioimmunoassay, a Western blot assay and a flow cytometry assay. ### Claim 56 (depends on 36) A method in accordance with claim 36, wherein the detecting comprises a flow cytometry assay. ### Claim 57 (depends on 34) A method in accordance with claim 34, wherein the at least one primary probe comprises a label, and the detecting presence, absence or quantity of the complex comprises quantifying the label. ### Claim 58 (depends on 57) A method in accordance with claim 57, wherein the label is selected from the group consisting of an enzyme, a radioisotope, a fluorogen, a fluorophore, a chromogen and a chromophore. ### Claim 59 (depends on 58) A method in accordance with claim 58, wherein the enzyme is selected from the group consisting of a peroxidase, a phosphatase, a galactosidase and a luciferase. ### Claim 60 (depends on 58) A method in accordance with claim 58, wherein the radioisotope is selected from the group consisting of a 32P, a 33P, 35S, a 14C, an 125I, an 131I and a 3H. ### Claim 61 (depends on 58) A method in accordance with claim 58, wherein the fluorophore is selected from the group consisting of a fluorescein, a rhodamine, an Alexa Fluor®, a coumarin, an indocyanine or a quantum dot a phycoerythrin, and a green fluorescent protein. ### Claim 62 (depends on 57) A method in accordance with claim 57, wherein the label is selected from the group consisting of a biotin, a digoxygenin, and a peptide comprising an epitope. ### Claim 63 (depends on 1) A method in accordance with claim 1, wherein the detecting presence, absence or quantity of a complex comprises: contacting the complex with at least one secondary probe that binds the at least one primary probe; and quantifying the at least one secondary probe bound to the complex, whereby if the sample comprises antibody against the Gammaretrovirus antigen, the quantity of the at least one secondary probe bound to the complex is less than the quantity of the at least one secondary probe bound to a complex formed from a mixture comprising a) the at least one Gammaretrovirus antigen, b) a control sample not comprising antibody against the at least one Gammaretrovirus antigen, and c) the competitive probe against the at least one Gammaretrovirus antigen. ### Claim 64 (depends on 63) A method in accordance with claim 63, wherein the quantifying the at least one secondary probe comprises an assay selected from the group consisting of an immunoprecipitation assay, an ELISA, a radioimmunoassay, a Western blot assay and a flow cytometry assay. ### Claim 65 (depends on 63) A method in accordance with claim 63, wherein the quantifying the at least one secondary probe comprises a flow cytometry assay. ### Claim 66 (depends on 1) A method in accordance with claim 1, further comprising selecting or modifying a treatment on the basis of the detection of antibody against XMRV in the sample. ### Claim 67 (depends on 66) A method in accordance with claim 66, wherein if antibody against XMRV is detected in the sample, the treatment comprises administrating to the subject a therapeutically effective amount of an anti-viral compound. ### Claim 68 (depends on 67) A method in accordance with claim 67, wherein the anti-viral compound is selected from the group consisting of acyclovir, penciclovir (famciclovir), gancyclovir (ganciclovir), deoxyguanosine, foscarnet, idoxuridine, trifluorothymidine, vidarabine, sorivudine, zidovudine, didanosine, zalcitabine, lamivudine, stavudine, abacavir, multinucleoside resistance A, multinucleoside resistance B, nevirapine, delavirdine, efavirenz, adefovir dipivoxil, indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, deoxycytosine triphosphate, lamivudine triphosphate, emticitabine triphosphate, adefovir diphosphate, penciclovir triphosphate, lobucavir triphosphate, amantadine, rimantadine, zanamivir and oseltamivir. ### Claim 69 A method of detecting, diagnosing, monitoring or managing an XMRV-related disease in a subject, the method comprising: providing a biological sample comprising antibody from the subject; forming a mixture comprising a) at least one Gammaretrovirus antigen and b) the sample, under conditions sufficient for formation of a complex comprising the at least one Gammaretrovirus antigen and antibody against the at least one Gammaretrovirus antigen if present in the antibody from the subject; and detecting presence, absence or quantity of a complex comprising the at least one Gammaretrovirus antigen and antibody against the at least one Gammaretrovirus antigen. ### Claim 70 (depends on 69) A method in accordance with claim 69, wherein the at least one Gammaretrovirus antigen is other than a gammaretrovirus gagp30. ### Claim 71 (depends on 69) A method in accordance with claim 69, wherein the method is other than a double antigen sandwich assay. ### Claim 72 (depends on 69) A method in accordance with claim 69, wherein the subject is a person having, suspected of having, or at risk for developing an XMRV-related disease. ### Claim 73 (depends on 72) A method in accordance with claim 72, wherein the XMRV-related disease is an XMRV-related prostate cancer. ### Claim 74 (depends on 72) A method in accordance with claim 72, wherein the XMRV-related disease is an XMRV-related lymphoma. ### Claim 75 (depends on 74) A method in accordance with claim 74, wherein the XMRV-related lymphoma is selected from the group consisting of a XMRV-related Mantle Cell Lymphoma (MCL) and an XMRV-related Chronic Lymphocytic Leukemia lymphoma (CLL). ### Claim 76 (depends on 72) A method in accordance with claim 72, wherein the XMRV-related disease is an XMRV-related neuroimmune disease. ### Claim 77 (depends on 76) A method in accordance with claim 76, wherein the XMRV-related neuroimmune disease is selected from the group consisting of chronic fatigue syndrome (CFS), Niemann-Pick Type C Disease, fibromyalgia, Multiple Sclerosis (MS), Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS) and autism. ### Claim 78 (depends on 77) A method in accordance with claim 77, wherein the Multiple Sclerosis is Atypical Multiple Sclerosis. ### Claim 79 (depends on 72) A method in accordance with claim 72, wherein the subject exhibits signs and/or symptoms of a neuroimmune disease and/or a lymphoma. ### Claim 80 (depends on 69) A method in accordance with claim 69, wherein the sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, and a cerebrospinal fluid sample. ### Claim 81 (depends on 61) A method in accordance with claim 61, wherein the blood sample is a peripheral blood sample. ### Claim 82 (depends on 69) A method in accordance with claim 69, wherein the at least one Gammaretrovirus antigen comprises a contiguous sequence of at least 4 amino acids of an XMRV polypeptide. ### Claim 83 (depends on 69) A method in accordance with claim 69, wherein the at least one Gammaretrovirus antigen is comprised by at least one cell ex vivo. ### Claim 84 (depends on 83) A method in accordance with claim 83, wherein the at least one cell ex vivo is a mammalian cell expressing at least one Gammaretrovirus antigen ex vivo. ### Claim 85 (depends on 84) A method in accordance with claim 84, wherein the mammalian cell expressing the at least one gammaretrovirus antigen is a BaF3ER cell. ### Claim 86 (depends on 84) A method in accordance with claim 84, wherein the mammalian cell expressing at least one Gammaretrovirus antigen is a BaF3ER-SFFVEnV cell expressing SFFV Env protein. ### Claim 87 (depends on 69) A method in accordance with claim 69, wherein the at least one Gammaretrovirus antigen is an SFFV antigen. ### Claim 88 (depends on 87) A method in accordance with claim 87, wherein the SFFV antigen is an SFFV Env antigen. ### Claim 89 (depends on 69) A method in accordance with claim 69, wherein the detecting presence, absence or quantity of a complex comprising the at least one Gammaretrovirus antigen and antibody against the at least one Gammaretrovirus antigen comprises contacting the mixture with at least one primary probe directed against antibody from the subject. ### Claim 90 (depends on 89) A method in accordance with claim 89, wherein the at least one primary probe is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, an aptamer, and an avimer. ### Claim 91 (depends on 89) A method in accordance with claim 89, wherein the at least one primary probe is an antibody or an antigen-binding fragment thereof. ### Claim 92 (depends on 91) A method in accordance with claim 91, wherein the antibody is a polyclonal antibody or a monoclonal antibody. ### Claim 93 (depends on 91) A method in accordance with claim 91, wherein the antigen-binding fragment is an Fab fragment. ### Claim 94 (depends on 91) A method in accordance with claim 91, wherein the antibody is an anti gp 55 Env antibody. ### Claim 95 (depends on 91) A method in accordance with claim 91, wherein the antibody is a monoclonal antibody MAb 7C10. ### Claim 96 (depends on 91) A method in accordance with claim 91, wherein the antibody is a polyclonal antibody against at least one Gammaretrovirus antigen. ### Claim 97 (depends on 91) A method in accordance with claim 91, wherein the detecting comprises an assay selected from the group consisting of an immunoprecipitation assay, an ELISA, a radioimmunoassay, a Western blot assay and a flow cytometry assay. ### Claim 98 (depends on 91) A method in accordance with claim 91, wherein the detecting comprises a flow cytometry assay. ### Claim 99 (depends on 89) A method in accordance with claim 89, wherein the at least one primary probe comprises a label, and the detecting presence, absence or quantity of a complex the comprises quantifying the label. ### Claim 100 (depends on 99) A method in accordance with claim 99, wherein the label is selected from the group consisting of an enzyme, a radioisotope, a fluorogen, a fluorophore, a chromogen and a chromophore. ### Claim 101 (depends on 100) A method in accordance with claim 100, wherein the enzyme is selected from the group consisting of a peroxidase, a phosphatase, a galactosidase and a luciferase. ### Claim 102 (depends on 100) A method in accordance with claim 100, wherein the radioisotope is selected from the group consisting of a 32P, a 33P, 35S, a 14C, an 125I, an 131I and a 3H. ### Claim 103 (depends on 99) A method in accordance with claim 99, wherein the label is selected from the group consisting of a biotin, a digoxygenin, and a peptide comprising an epitope. ### Claim 104 (depends on 69) A method in accordance with claim 69, wherein the detecting presence, absence or quantity of a complex comprises: contacting the complex with at least one secondary probe that binds the at least one primary probe; and quantifying the at least one secondary probe. ### Claim 105 (depends on 104) A method in accordance with claim 104, wherein the quantifying comprises an assay selected from the group consisting of an immunoprecipitation assay, an ELISA, a radioimmunoassay, a Western blot assay and a flow cytometry assay. ### Claim 106 (depends on 104) A method in accordance with claim 104, further comprising selecting or modifying a treatment on the basis of the detection of antibody against XMRV in the sample. ### Claim 107 (depends on 106) A method in accordance with claim 106, wherein if antibody against XMRV is detected in the sample, the treatment comprises administrating to the subject a therapeutically effective amount of an anti-viral compound. ### Claim 108 (depends on 107) A method in accordance with claim 107, wherein the anti-viral compound is selected from the group consisting of acyclovir, penciclovir (famciclovir), gancyclovir (ganciclovir), deoxyguanosine, foscarnet, idoxuridine, trifluorothymidine, vidarabine, sorivudine, zidovudine, didanosine, zalcitabine, lamivudine, stavudine, abacavir, multinucleoside resistance A, multinucleoside resistance B, nevirapine, delavirdine, efavirenz, adefovir dipivoxil, indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, deoxycytosine triphosphate, lamivudine triphosphate, emticitabine triphosphate, adefovir diphosphate, penciclovir triphosphate, lobucavir triphosphate, amantadine, rimantadine, zanamivir and oseltamivir.