Animal Models and Therapeutic Molecules

摘要

The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

主权项

1. A method of providing a transgenic mouse ES cell comprising unrearranged human IgH VH, D, and JH gene segments in its genome, the method comprising serially inserting a plurality of human DNA fragments comprising unrearranged human IgH variable region gene segments into the genome of a mouse ES cell, comprising the following steps:
inserting into a mouse ES cell genome at a position upstream of an endogenous IgH constant (C) gene segment a first human DNA fragment comprising a human DJH fragment comprising unrearranged human D gene segments and human JH gene segments, thereby to provide a mouse ES cell comprising a genome comprising said inserted human DJH fragment; and inserting into a mouse ES cell genome comprising said inserted human DJH fragment a second human DNA fragment comprising a human VH fragment comprising unrearranged human IgH V gene segments such that said inserted human DJH fragment and said human VH fragment form a contiguous inserted human DNA comprising unrearranged human IgH VH, D, and JH gene segments, thereby to provide a transfected mouse ES cell comprising in its genome said unrearranged human IgH VH, D, JH gene segments positioned upstream of, and in functional arrangement with, said endogenous IgH C gene segment.