Amgen Fremont Inc.

Abgenix, Inc.

Vladimir E Ivanov

Larry L Green

C Geoffrey Davis

Geoffrey C Davis

The present invention provides fully human antibodies in a transgenic animal of a desired isotype in response to immunization with any virtually any desired antigen. The human immunoglobulin heavy chain transgene in the foregoing animals comprises a human constant region gene segment comprising exons encoding the desired heavy chain isotype, operably linked to switch segments from a constant region of a different heavy chain isotype, i.e., a non-cognate switch region. Said additional constant region segment comprises a switch region and human constant region coding segment, wherein the constant region coding segment is operably linked to a switch region that it is not normally associated with, i.e., a non-cognate switch region. In the transgenes of the invention, the non-cognate switch region may be a switch region from a different species than the constant region coding segment. The switch region and membrane exons of the invention may comprise a human gamma-2 constant region and the secreted constant region exons are from a human gamma-1 or a human gamma-4 constant region.

Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions

The invention relates to transgenic animals bearing one or more human &#x3bb; light chain loci. The invention also relates to methods and compositions for making transgenic animals that have incorporated human &#x3bb; light chain loci. The invention further relates to methods of using and compositions derived from the transgenic animals that have incorporated human &#x3bb; light chain loci.

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Fremont, CA, United States of America

Vladimir E Ivanov