C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/13 (2006.01) A01K 67/027 (2006.01) C07K 16/00 (2006.01) C07K 16/46 (2006.01) C12N 5/10 (2006.01) C12N 5/20 (2006.01) C12N 15/85 (2006.01) C12P 21/08 (2006.01)
Patent
CA 2124967
The invention relates 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 immunoglob-ulin genes are suppresed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. He-terologous 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 heterogolous human immu-noglobulin 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 hu-man 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 immunog-lobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous im-munogiobulin loci in the transgenic animal.
Kay Robert M.
Lonberg Nils
Genpharm International Inc.
Smart & Biggar
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