Human antibodies

A method of producing a human Fab phage display library, comprising:

• providing a transgenic mouse whose genome comprises a plurality of human immunoglobulin genes that can be expressed to produce a plurality of human antibodies, wherein the transgenic mouse comprises less than the full complement of human immunoglobulin genes present in a human being;
• isolating populations of nucleic acids respectively encoding human antibody heavy chains and human antibody light chains from lymphatic cells of the transgenic mouse by amplifying the populations of nucleic acids using a set of primers selected based on which human immunoglobulin genes from the full complement of human immunoglobulin genes are present in the genome of the transgenic mouse;
• cloning the populations into multiple copies of a phage display vector to produce a display library, wherein a library member comprises a phage capable of displaying from its outersurface a fusion protein comprising a phage coat protein, a human antibody light chain or human antibody heavy chain, wherein in at least some members, the human antibody heavy or light chain is complexed with a partner human antibody heavy or light chain, the complex forming a Fab fragment to be screened, wherein the library comprises at least 100 members at least 50% of which comprise nucleic acids encoding Fab fragments showing at least 109M−1 affinity for the same target and no library member constitutes more than 50% of the library.