Ransgenic non-human animals for producing heterologous antibodie

Details Ransgenic non-human animals for producing heterologous antibodie Ransgenic non-human animals for producing heterologous antibodie

1992-12-16

1996-08-13

Ziska, Suzanne E.

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

800DIG1, 800DIG4, 536 2353, 536 235, 536 231, 4241841, 4351723, 4353201, C12N 1500, C07H 2164, A61K 3900

Patent

active

055458068

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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