McWhirter, John,MacDonald, Lynn,Stevens, Sean,Davis, Samuel,Murphy, Andrew J.,Buckler, David R.
申请号:
ES12173456
公开号:
ES2603559T3
申请日:
2011.02.08
申请国别(地区):
ES
年份:
2017
代理人:
摘要:
A genetically modified mouse that expresses human immunoglobulin light and heavy chain variable human domains, where human light chain variable domains are expressed from a single gene sequence of human immunoglobulin (VL / JL) light chain variable region present in the mouse germline comprising a germline sequence of a genetic segment VL and a germline sequence of a genetic segment JL, said human immunoglobulin light chain variable region being a rearranged Vκ 1-39 / Jκ, where: (a) the mouse lacks a κ light chain variable region locus of mouse immunoglobulin that is capable of rearranging and forming a gene encoding a mouse κ variable region; (b) the mouse expresses a common human immunoglobulin light chain for a plurality of human heavy chains, derived from the common light chain of said human immunoglobulin light chain variable region genetic sequence; (c) the mouse comprises a B cell that expresses an antibody that specifically binds to an antigen of interest, wherein the antibody comprises said common light chain and an immunoglobulin heavy chain of a rearrangement of heavy chain variable genetic segments (VH) of human immunoglobulin that are selected from the group consisting of a genetic segment VH2-5, VH3-23, VH3-30, VH4-59, and VH5-51; and (d) 90-100% of the mouse endogenous mouse rearranged VH genetic segments are replaced with a plurality of rearranged human VH genetic segments.Un ratón modificado genéticamente que expresa dominios variables humanos de cadena ligera y pesada de inmunoglobulina, donde los dominios variables de cadena ligera humana se expresan a partir de una única secuencia genética de región variable de cadena ligera de inmunoglobulina humana (VL/JL) reordenada presente en la línea germinal del ratón que comprende una secuencia de línea germinal de un segmento genético VL y una secuencia de la línea germinal de un segmento genético JL, estando dicha región variable de cadena ligera de inmunoglobulina humana una Vκ 1-39/Jκ reordenada, dond