Abstract: A method for producing immortalized antibody-secreting cells, comprising: (a) providing a transgenic animal having antibody-secreting cells capable of expressing one or more transgenes, wherein the antibody-secreting cells are in a non-immortalized state in the absence of a stimulus and are capable of changing to an immortalized state by means of the transgene or transgenes upon exposure of the cells to the stimulus; (b) extracting the antibody-secreting cells from the animal; and (c) exposing the antibody-secreting cells to the stimulus, thereby immortalizing the antibody secreting cells by means of the transgene or transgenes.

Abstract: The invention provides, in part, methods for the production of proteins in a transgenic non-human mammal, wherein the proteins are transported from the blood to the mammary gland for secretion in milk. The transport of the protein to the mammary gland and/or milk is facilitated by binding to a transport receptor in the mammary gland.

Abstract: A non-human animal that produces human tissue factor (TF) without substantially producing non-human animal tissue factor, said animal having a genome in which cDNA encoding human TF has been inserted upstream of the translation initiation codon for the non-human animal genomic TF gene.

Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Abstract: It is an object of the present invention to provide a high affinity antibody effective as a diagnostic or therapeutic for various diseases; a transgenic mammal for producing the high affinity antibody; and a medicine comprising the high affinity antibody or a cell producing the high affinity antibody. According to the present invention, a transgenic mammal carrying a GANP gene transferred thereinto, its progeny, or a part thereof, and a method of producing a high affinity antibody using the same are provided.

Abstract: The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Abstract: The present invention relates to the use of antibodies against glucose-6-phosphate isomerase (GPI) and like protein for diagnosis of arthritis and the use of said protein for treatment of arthritis. It is also aimed at a process for isolating monoclonal antibodies capable of transferring arthritis and antibodies thereof, as well as a method for determining the anti-arthritis potential of a composition.

Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: The present invention has for its object to provide a transgenic bird with a foreign gene containing a feline-derived protein-encoding sequence as transferred therein, and a method of producing the same. The present invention provides a method of producing a feline-derived protein by using a transgenic bird with a method which comprises infecting an avian embryo with a replication defective retrovirus vector containing a foreign gene by microinjection thereof into the early heart or blood vessel formed in the embryo and allowing the embryo to hatch.

Abstract: The present invention has its object to provide a transgenic bird producing erythropoietin at high concentration levels as well as a method for constructing the same. The present invention provides a G0 transgenic chimera bird as obtained by incubating a fertilized avian egg, infecting the early embryo formed after egg laying, except for the blastoderm stage immediately following egg laying, with a replication-deficient retroviral vector containing a foreign erythropoietin gene and allowing the embryo to hatch.

Abstract: Modified fission proteins of transferrin and therapeutic proteins or peptides, preferably antibody variable regions, with increased serum half-life or serum stability are disclosed. Preferred fusion proteins include those modified so that the transferrin moiety exhibits no or reduced glycosylation, binding to iron and/or binding to the transferrin receptor.

Abstract: The invention relates to novel polypeptides which have the biological activity of an NAD- or NADP-dependent alcohol dehydrogenase. The invention furthermore relates to nucleic acids encoding said polypeptides, to non-human hosts or host cells and to reaction systems which may be used for preparing desired products. The polypeptides of the invention are preferably used in the preparation, starting from aldehydes or ketones, of primary and enantiomerically pure secondary alcohol's which may serve as intermediates for medicaments. Alternatively, the polypeptides of the invention may also be employed in the reverse reaction, i.e. the oxidation of alcohol's with the formation of aldehydes or ketones.

Abstract: The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Abstract: The specification provides methods of preparing high-affinity antibodies to a macrophage migration inhibitory factor (MIF) in animals in which the MIF gene has been homozygously knocked-out (MIF?/?). Also provided are methods of preparing hybridomas which produce the anti-MIF antibodies, methods of administering the antibodies to treat inflammatory or cancerous conditions and/or diseases modulated by MIF, as well as compositions comprising said high-affinity anti-MIF antibodies.

Abstract: The invention relates to a method for producing a protein of interest comprising transforming a target insect with a non-viral expression system that expresses the protein in the insect larvae, breeding the insect to produce larvae, culturing the larvae and isolating the protein from the larvae.

Abstract: The subject invention relates a method for the production of monoclonal antibodies. The method utilizes an immunized animal having antibody-producing cells with disrupted peripheral tolerance. The invention also provides a method for the use of such monoclonal antibodies, and polyclonal antibodies derived from an immunized animal having antibody-producing cells with disrupted peripheral tolerance, for in vitro and in vivo clinical diagnostics and therapeutics.

Abstract: The invention is directed to methods of producing a protein by administering a nucleic acid encoding the protein to an animal. Following the administration of the nucleic acid to the animal, the protein is produced in vivo and is isolated by removing a biological sample from the animal. These methods allow for the rapid and efficient production and isolation of a protein encoded by any nucleic acid sequence of interest and can be used to generate antibodies that bind to the protein sequence.

Abstract: A chimeric, non-human animal can be produced by a method that entails providing a microcell that contains one or more foreign chromosomes or fragment(s) thereof and then fusing the microcell with a pluripotent cell, thereby introducing the foreign chromosome(s) or fragment(s) into the latter. The pluripotent cell thus obtained can be used to generate a chimeric, non-human animal, the cells, tissues, and/or progeny of which can be the source of a product, such as an antibody, that is associated with one or more genes on the foreign chromosome(s) or fragment(s).

Abstract: The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the &bgr;-globin locus are sufficient to result in high level expression of human &agr;- or &bgr;-globin transgenes.

Abstract: The present invention relates to novel human coagulation Factor VIIa variants having coagulant activity as well as polynucleotide constructs encoding such variants, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.

Abstract: A culture system for producing PGCs or EG cells by culturing PGCs for long periods in tissue culture is provided. This culture system uses LIF, bFGF, IGF and SCF. The resultant EG cells are useful for the production of transgenic and chimeric avians, in particular, chickens and turkeys, and also for cloning purposes.

Abstract: Transgenic mice that produce high levels of humanized antibodies are described. Targeted gene replacement exchanges constant regions of the mouse immunoglobulin heavy and light chain genes with human genes, either through conventional gene targeting, or by use of the bacteriophage-derived Cre-loxP recombination system. The transgenic animals undergo antibody affinity maturation, and a class switch from the native immunoglobulin to the humanized form.

Abstract: A non-liposome based linker such as an antibody is disclosed for use attached nucleic acid molecules to sperm cells. The antibody is characterized by having binding affinity to a sperm cell and wherein the sperm cell bound with the antibody retains the ability to fertilize an oocyte. A resulting sperm-linker-nucleic acid complex may- be used to generate genetically modified animals and cells by in vitro or in vivo fertilization with an egg cell. Introduction of exogenous DNA using this method in various animals (mice, pigs, chickens, and cows) are disclosed. Functional screening of gene with unknown function may also be performed using the disclosed method.

Abstract: A transgenic animal with alterations in an H2-O gene is prepared by introduction of an altered H2-O gene into a host animal. The resulting transgenic animals produce a substantially greater frequency of high affinity antibodies compared to H2-O wild type animals. A method for the production of high affinity antibodies is disclosed.

Abstract: The present invention provides a method of biasing the immune response of a mammal toward a desired epitope of a chosen antigen, particularly a functionally-relevant epitope. In preferred embodiments, the epitope-biasing method leads to fully-human antibodies of defined specificity with affinities of 10 nM to 50 pM. The invention further provides antibody libraries biased to tissues and to cell types, for use in generating epitope expression profiles useful for characterizing unknown genes. When all aspects of the present invention are combined, they result in an integrated system for defining critical epitopes on newly discovered gene products and rapidly devloping therapeutic grade antibodies to those critical epitopes.

Abstract: The present invention describes a non-human transgenic mammal that produces in its leukocytes, a recombinant human leukotriene B4 receptor (BLTR), having physiological activity of human BLTR. The transgenic mammal has stably integrated into its genome an exogenous gene construct which includes (A) 5′ expression regulating sequences, including a BLTR specific promoter, (B) DNA encoding the BLTR and a signal sequence effective in directing overexpression of the BLTR into leukocytes of the transgenic mammal and (C) 3′ regulatory sequences that result in the overexpression of the DNA in the leukocytes. In one embodiment, (A), (B), and (C) are operably linked in the gene construct to obtain production of the BLTR in the leukocytes and overexpression thereof in the transgenic mammal.

Abstract: The present invention features a novel cellular injury reporter system in which a chimeric gene containing the GADD153 promoter linked to the coding region of an enhanced green fluorescent protein (EGFP) gene was stably integrated into the genome of carcinoma cells. Activation of the GADD153 promoter was quantified using flow cytometric measurement of EGFP expression following drug exposure. This reporter system is suitable for high throughput in vitro and in vivo screening for agents capable of producing cytotoxicity via a wide variety of different mechanisms, and can be utilized to investigate the relative potency of structurally related DNA adducts.

Abstract: The present invention provides novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The present invention also provides for the transgenic animals which contain these recombinant nucleic acid vectors. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. According to various embodiments of the invention, the vectors may be used to create transgenic animals or to transfect cells in culture. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.-globin protein in erythroid tissues, including red blood cells.

Abstract: Transgenes for producing recombinant polypeptides transgenic bovine species. A transgene for producing recombinant polypeptides in the milk of transgenic bovine species comprises at least one expression regulation sequence, a secretory DNA sequence encoding a secretory signal sequence which is functional in mammary secretory cells of the bovine species and a recombinant DNA sequence encoding the recombinant polypeptide. Also included are methods for producing transgenic bovine species. The method includes introducing the above transgene into an embryonal target cell of a bovine species, transplanting the transgenic embryonic target cell formed thereby into a recipient bovine parent and identifying at least one female offspring which is capable of producing the recombinant polypeptide in its milk.