- Patent Title: System and products for improved quantification of ADCC activity
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Application No.: US16339327Application Date: 2017-03-10
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Publication No.: US11280790B2Publication Date: 2022-03-22
- Inventor: Michael Tovey , Christophe Lallemand
- Applicant: SVAR LIFE SCIENCE AB
- Applicant Address: SE Malmö
- Assignee: SVAR LIFE SCIENCE AB
- Current Assignee: SVAR LIFE SCIENCE AB
- Current Assignee Address: SE Malmö
- Agency: Casimir Jones, S.C.
- Agent Lisa Mueller
- Priority: EP16192246 20161004
- International Application: PCT/EP2017/075053 WO 20170310
- International Announcement: WO2018/065401 WO 20180412
- Main IPC: G01N33/569
- IPC: G01N33/569 ; C12N9/22 ; C12N15/86 ; G01N33/50 ; C12N15/63

Abstract:
The activity of a number of therapeutic antibodies is mediated in part by antibody-dependent cell-mediated cytotoxicity (ADCC). An engineered effector cell line expressing the low affinity Fc receptor, FcγR111a (CD16), that responds to ligation of the Fc moiety of antibody bound to the specific antigen expressed on target cells by activation of a NFAT responsive reporter gene is described. In this cell line the firefly luciferase (FL) reporter gene is regulated by a novel synthetic chimeric promoter containing binding sites for NF-AT, AP1, NFkB, and STAT5 that confers improved sensitivity, an improved dynamic range, an improved tolerance to human serum and a reduced incubation time, relative to engineered effector cell lines that express a NFAT regulated reporter-gene, when used in an ADCC assay together with engineered target cells. The target cells have been engineered to over-express a constant high level of the specific antigen recognized by the therapeutic antibody, and homologous control cells have been developed in which the gene encoding the specific drug target has been invalidated by genomic editing. Target cells that have been engineered to over-express a constant level of CD20 together with homologous control cell line, in which the gene encoding CD20 has been invalidated, have been used to quantify the ADCC activity of Rituxan with a high degree of precision and with minimal interference from human serum.
Public/Granted literature
- US20190310251A1 SYSTEM AND PRODUCTS FOR IMPROVED QUANTIFICATION OF ADCC ACTIVITY Public/Granted day:2019-10-10
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