05661016 is referenced by 833 patents and cites 14 patents.

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.

Title
Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
Application Number
574748
Publication Number
5661016
Application Date
April 26, 1993
Publication Date
August 26, 1997
Inventor
Robert M Kay
San Francisco
CA, US
Nils Lonberg
San Francisco
CA, US
Agent
Townsend and Townsend and Crew
Assignee
GenPharm International
CA, US
IPC
C07K 16/00
C12P 19/34
A61K 39/00
C12N 15/00
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