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Cytokine biomarkers as predictive biomarkers of clinical response for glatiramer acetate
专利权人:
TEVA PHARMACEUTICAL INDUSTRIES LTD.
发明人:
KASPER LLOYD H.,SMITH JACQUELINE Y.
申请号:
NZ70312211
公开号:
NZ703122A
申请日:
2011.10.10
申请国别(地区):
NZ
年份:
2016
代理人:
摘要:
method of predicting clinical responsiveness to glatiramer acetate therapy in a human subject afflicted with multiple sclerosis or a single clinical attack consistent with multiple sclerosis comprises evaluating a biomarker selected from the group consisting of IL-17 concentration, TNF-alpha concentration, IL-2 concentration and IFN-gamma concentration, or a combination thereof, in the supernatant of PBMCs derived from the subject’s blood, and identifying the human subject as a glatiramer acetate responder based on the biomarker. The subject can be identified as a glatiramer acetate responder by steps comprising i) purifying PBMCs from the subject’s blood and then cryopreserving the PBMCs; ii)thawing and then culturing the cryopreserved PBMCs overnight in culture medium supplemented with 5% human serum; iii) stimulating 40,000 of said cultured PBMCs with 1 mg/ml PMA and 5 mg/ml ionomycin in a final volume of 200 microliters for 6 hours; and iv) identifying the human subject as a glatiramer acetate responder a)if the IL-17 concentration of the supernatant of PBMCs after step (iii) is greater than or equal to 120 pg/ml, b) if the TNF-a concentration of the supernatant of PBMCs after step (iii) is greater than or equal to 20000 pg/ml, c) if the IFN-y concentration of the supernatant of PBMCs after step (iii) is greater than or equal to 6000 pg/ml, or d) if the IL-2 concentration of the supernatant of PBMCs after step (iii) is greater than or equal to 30000 pg/ml, thereby predicting clinical responsiveness to glatiramer acetate.
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