Stem Cell Related Patent Number US6162963

Generation of Xenogenetic antibodies

Kucherlapati, Raju; Darien, CT, USA
Jakobovits, Aya; Menlo Park, CA, USA
Klapholz, Sue; Stanford, CA, USA
Brenner, Daniel G.; Redwood City, CA, USA
Capon, Daniel J.; Hillsborough, CA, USA

Described herein are methods of modifying the genome of embryonic stem cells via the use of yeast spheroplasts containing a yeast artificial chromosome with a xenogeneic DNA segment. Products of the invention include a transgenic mouse lacking expression of an endogenous immunoglobulin light chain, namely, an inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. Strategies of recombination are provided, as are properties of the resulting chimeric and transgenic nonhuman mammals with stably integrated large, xenogeneic DNA segments which have been introduced by fusion with the yeast spheroplasts that contain the yeast artificial chromosomes (YACs) and which further include the xenogeneic DNA segments and a selective marker such as HPRT in addition to embryonic stem cells. Therapeutic applications in the treatment of human diseases with such antibodies are included.

Application Number: US1995000462513

Date Filed: 06/05/95

Dated Published: 12/19/00

Assignee: Abgenix, Inc., Fremont, CA, USA