Transgenic non-human animals for producing heterologous antibodi

Details Transgenic non-human animals for producing heterologous antibodi Transgenic non-human animals for producing heterologous antibodi

1992-03-18

1998-08-04

Ziska, Suzanne E.

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

4351723, 5303871, 536 2653, 800DIG1, 800DIG2, 800DIG4, C12N 1500, C07K 1600, C07H 1904

Patent

active

057896500

ABSTRACT:
The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin 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 of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of 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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