Transgenic non-human animals capable of producing heterologous a

Details Transgenic non-human animals capable of producing heterologous a Transgenic non-human animals capable of producing heterologous a

1991-12-17

1996-10-29

Ziska, Suzanne E.

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

4351723, 4353201, 536 2353, 800DIG1, C12N 1500, C07H 2104

Patent

active

055698255

ABSTRACT:
The invention relates to transgenic non-human animals capable of producing heterologous antibodies of multiple isotypes. Heterologous antibodies are encoded by immunoglobulin heavy chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences that permit isotype switching of encoded unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.

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