BRADLEY, Allan,FRIEDRICH, Glenn,LEE, E-Chiang,STRIVENS, Mark,ENGLAND, Nicholas
申请号：
ES12772122
公开号：
ES2612935T3
申请日:
2012.09.18
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A method for producing a heavy chain, a VH domain or an antibody specific for a target antigen, wherein the heavy chain, the VH domain or the antibody comprises an HCDR3 of at least 20 amino acids in length, the method comprising providing a non-vertebrate human, optionally a mouse or a rat, having a genome comprising an immunoglobulin heavy chain locus comprising a segment of a non-rearranged human JH6 * 02 gene, one or more segments of the VH gene and one or more segments of the gene D upstream of a constant region； wherein the gene segments in the heavy chain locus are operably connected to the constant region thereof so that the vertebrate is capable of producing an antibody heavy chain produced by recombination of human JH6 * 02 with a segment of D human and a human VH segment, where the JH6 * 02 gene segment comprises the following nucleotide sequence: ATTACTA CTACTACTAC GGTATGGACG TCTGGGGCCA AGGGACCACG GTCACCGTCT CCTCAG, and where the vertebrate has been immunized with the target antigen and produces a heavy chain of specific antibody to the target antigen where the heavy chain variable domain is the product of recombination between a human VH, D and JH6 * 02 and where the length of the HCDR3 is at least 20 amino acids, and isolate from the vertebrate non-human heavy chain, the VH domain or an antibody specific for the target antigen or a heavy chain producing cell, the VH domain or the antibody, wherein the heavy chain, the VH domain or the antibody comprises an HCDR3 that derives from the recombination of human JH6 * 02 with a segment of the human VH gene and a segment of the human D gene, optionally wherein the constant region of the locus is a constant region of the non-human vertebrate (e.g. eg, mouse or rat), and the non-human constant region of the isolated heavy chain or antibody is replaced by a human constant region.Un método para producir una cadena pesada, un dominio VH o un anticuerpo específicos para un antígeno diana, en donde la cadena pesada,
