Patent
Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
Nils Lonberg,Robert M. Kay +1 more
TLDR
In this article, a 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 transgenio-globulin sequences and producing a repertoire of antibodies.Abstract:
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.read more
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Patent
Transgenic non-human animals capable of producing heterologous antibodies
Nils Lonberg,Robert M. Kay +1 more
TL;DR: In this paper, a transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity are described.
Patent
Human antibodies derived from immunized xenomice
TL;DR: In this paper, a transgenic animal has been modified to produce antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, and various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
Patent
Generation of xenogeneic antibodies
Raju Kucherlapati,Aya Jakobovits +1 more
TL;DR: In this article, the subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human ICLs for response to an immunogen to produce human antibodies or analogs thereof.
Patent
Secreted and Transmembrane Polypeptides and Nucleic Acids Encoding the Same
Kevin P. Baker,Maureen Beresini,Laura DeForge,Luc Desnoyers,Ellen Filvaroff,Wei-Qiang Gao,Mary E. Gerritsen,Audrey Goddard,Paul J. Godowski,Austin L. Gurney,Steven Sherwood,Victoria Smith,Timothy A. Stewart,Daniel Tumas,Colin K. Watanabe,William I. Wood,Zemin Zhang +16 more
TL;DR: In this paper, the present invention is directed to secreted and transmembrane polypeptides and to nucleic acid molecules encoding those polyptides, and vectors and host cells comprising those nucleic amino acid sequences.
Patent
Transgenic mammals having human Ig loci including plural VH and VK regions and antibodies produced therefrom
TL;DR: In this paper, a transgenic non-human animal was engineered to contain human immunoglobulin gene loci, including plural variable (V H and Vκ) gene regions.
References
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Patent
Process for amplifying, detecting, and/or-cloning nucleic acid sequences
Kary Banks Mullis,Norman Arnheim,Randall K. Saiki,Henry A. Erlich,Glenn Thomas Horn,Stephen J. Scharf +5 more
TL;DR: In this paper, the authors proposed a method for synthesizing nucleic acid sequences using primers, which can be repeated stepwise or simultaneously and can be replicated as often as desired.
Patent
Transgenic non-human animals capable of producing heterologous antibodies
Nils Lonberg,Robert M. Kay +1 more
TL;DR: In this paper, a transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity are described.
Journal ArticleDOI
Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
Kirk R. Thomas,Mario R. Capecchi +1 more
TL;DR: This work mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells and compared the gene-targeting efficiencies of two classes of neor-Hprt recombinant vectors.
Journal ArticleDOI
Altering the genome by homologous recombination.
TL;DR: The current status of gene targeting with particular emphasis on germ line modification of the mouse genome is discussed, and the different methods so far employed to identify those rare embryonic stem cells in which the desired targeting event has occurred are described.
Journal ArticleDOI
Antisense oligonucleotides: a new therapeutic principle
Eugen Uhlmann,Anusch Peyman +1 more