Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6162963

Title:Generation of Xenogenetic antibodies
Inventors: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
Summary: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.
Abstract:The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6162963
Application Number:US1995000462513
Date Filed:05/06/1995
Date Published:19/12/2000
Assignee:Abgenix, Inc., Fremont, CA, USA


 
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