Abstract: The present invention relates to a method for the generation of single chain immunoglobulins in a mammal. In particular, the present invention relates to a method for the generation of single chain camelid VHH antibodies in a mammal which undergo the process of class-switching and affinity maturation found within antibody producing B cells. Single chain antibodies generated using the method of the present invention and the uses thereof are also described.

Abstract: The invention provides methods for producing a plurality of monoclonal antibodies, which plurality contains an antibody for each member of a plurality of different antigens. In general, the methods involve administering a plurality of antigens or a cellular immunogen made up of a cell population expressing a plurality of antigens to a single animal to induce an immune response against the plurality of antigens, and producing monoclonal antibodies from antibody-producing cells of the animal. In general, the antigens expressed by the cells of the cellular immunogen are not native to the cells, and the cells are derived from the same species as the host. The invention further provides screening methods for identifying monoclonal antibodies of interest, and kits for carrying out the subject methods. The subjects systems, methods and kits find use in a variety of different industrial, medical and research applications.

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.

Abstract: The present invention provides an antibody composition which specifically binds to CD20 and comprises an antibody molecule which has complex N-glycoside-linked sugar chains bound to the Fc region; a process for producing the antibody composition; and a medicament comprising the antibody composition.

Abstract: The present invention relates to antibodies immunologically specific for an attaching and effacing Escherichia coli (AEEC) virulence-associated protein, products, compositions and methods and to their use thereof in the prevention of an AEEC infection in a mammal. The antibody of the invention is immunologically specific for an AEEC virulence-associated protein and is capable of preventing an in vivo AEEC intestinal infection when administered to a mammal. The antibody of the invention is preferably useful for preventing the development of A/E intestinal lesions associated with the AEEC. This is achieved by preferably using IgY antibodies immunologically specific for one or more AEEC virulence-associated proteins, such as Eae, Tir, EspA and Paa.

Abstract: The specification relates to a method for producing a chimeric non-human animal, which comprises preparing a microcell containing a foreign chromosome(s) or a fragment(s) thereof and transferring the foreign chromosome(s) or fragment(s) thereof into a pluripotent cell by fusion with the microcell; a chimeric non-human animal which can be produced by the above method and its progeny; tissues and cells derived therefrom; and a method for using the same. Further, a pluripotent cell containing a foreign chromosome(s) or a fragment(s) thereof, a method for producing the same, and a method for using the same are also provided. Moreover, a pluripotent cell in which at least two endogenous genes are disrupted, and a method for producing the same by homologous recombination 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 invention provides isolated defense-inducible nucleic acids and their encoded proteins. The present invention provides methods and compositions relating to altering the concentration and/or composition of plants. The invention further provides recombinant expression cassettes, host cells, and transgenic plants.

Abstract: The present invention provides for the production of homozygous primary cells that carry a specific transgenic integration of interest on both chromosomes by bypassing breeding. These cell lines can they be used for the accelerated production of homozygous transgenic animals by somatic cell nuclear transfer. The invention is thus useful in the production of transgenic ungulate animals capable of producing desired biopharmaceuticals in their milk at higher yield than a comparable heterzygote. By combining the selection techniques of the current invention with somatic cell nuclear transfer it can be applied to large animals, where there is a strong need to shorten the time to homozygosity.

Abstract: A novel gene (designated 121P2A3) and its encoded protein, and variants thereof, are described wherein 121P2A3 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 121P2A3 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 121P2A3 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 121P2A3 can be used in active or passive immunization.

Abstract: A novel gene (designated 213P1F11) and its encoded protein, and variants thereof, are described wherein 213P1F11 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 213P1F11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 213P1F11 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 213P1F11 can be used in active or passive immunization.

Abstract: A novel gene (designated 238P1B2) and its encoded protein, and variants thereof, are described wherein 238P1B2 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 238P1B2 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 238P1B2 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 238P1B2 can be used in active or passive immunization.

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.

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: A novel gene (designated 161P5C5) and its encoded protein, and variants thereof, are described wherein 161P5C5 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 161P5C5 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 161P5C5 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 161P5C5 can be used in active or passive immunization.

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.

Abstract: A novel gene (designated 193P1E1B) and its encoded protein, and variants thereof, are described wherein 193P1E1B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 193P1E1B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 193P1E1B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 191P1E1B can be used in active or passive immunization.

Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: This invention includes methods for producing non-human mammals expressing monoclonal or oligoclonal B or T lymphocytes, as well as embryonic and hematopoietic stem cells that differentiate into monoclonal or oligoclonal B or T cells, using cloning by nuclear transfer with a B or T cell of interest as the nuclear donor cell.

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

Abstract: Methods are described to obtain nucleic acid molecules that encode T cell receptors and their derivatives that are human HLA-restricted and which are specific for tumor-associated antigens found in human tumors. These nucleic acids are useful in preparing recombinant cells for diagnosis and therapy of human tumors.

Abstract: 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.

Abstract: A novel gene 0161P2F10B (also designated 161P2F10B) and its encoded protein, and variants thereof, are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, and is aberranty expressed in the cancers listed in Table I. Consequently, 161P2F10B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 161P2F10B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 161P2F10B can be used in active or passive immunization.

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 invention features compositions containing avian-derived transgenic non-avian antibodies and methods of recovering the compositions from transgenic avian eggs. Chromatographic techniques permit the purification of non-avain proteins produced in an avain tissue from contaminating avian tissue components for administration to humans.

Abstract: Transgenes encoding exogenous proteins are stably integrated into embryonic stem cells and are present in the somatic tissue of transgenic or chimeric birds. The transgenes encode exogenous proteins and are expressed in any of endodermal, ectodermal, mesodermal, or extra embryonic tissue. Tissue specificity is provided by selecting the content of the transgene accordingly. Transgenic birds whose genome is comprised of trangene derived exogenous DNA express exogenous proteins with tissue specificity, and specifically express exogenous proteins in the tubular gland cells of the oviduct to concentrate exogenous proteins in egg white..

Abstract: A protein obtainable from a non pathogenic microorganism, said protein having mucosa binding promoting activity and a molecular weight of 20-40 kD is disclosed. Application of such a protein or a peptide derived therefrom in a method of screening non pathogenic microorganisms for a microorganism capable of specifically binding mucosa, said method comprising detection in a manner known per se of the presence of a particular protein on or in a microorganism or in a culture of microorganisms, said particular protein being the already defined protein. Kits suitable for such a screening method are also disclosed.

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 invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

Abstract: There are disclosed mammary gland tissue-specific expression systems using the promoter site for the &bgr;-casein gene of Korean native goats, by use of which physiological activating substances can be produced. In each of the expression systems, that is, novel plasmids pGbc, pGbc_L and pGbc_S (deposition Nos. KCTC 0515BP, 0514BP and 0513BP, respectively), a &bgr;-casein gene expression-regulating region, a physiological activating substance gene and a termination-regulating region are linked. Human granulocyte colony stimulating factor (hG-CSF) or human granulocyte macrophage colony stimulating factor (hGM-CSF) can be produced in HC11 cells, a mouse mammary gland tissue-derived cell line, and in the milk secreted from the transgenic mice by use of a hG-CSF or hGM-CSF gene-carrying pGbc, pGbc_L or pGbc_S in transfection into cell and microinjection to mouse. The proteins are those which experience the posttranslational modification and maintain their normal activity in the human body.

Abstract: The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

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: 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 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 relates to the production of a transgenic bovine which comprises a genetic modification that results in inactivation and loss of expression of its endogenous antibodies, and the expression of xenogenous antibodies, preferably human antibodies. This is effected by inactivation of the IgM heavy chain expression and, optionally, by inactivation of the Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of non-bovine antibodies, preferably human antibodies.

Abstract: Methods for preparing cell lines and transgenic animals that contain artificial chromosomes, methods for preparation of artificial chromosomes, methods for purification of artificial chromosomes, methods for targeted insertion of heterologous DNA into artificial chromosomes, and methods for delivery of the chromosomes to selected cells and tissues are provided. Also provided are cell lines for use in the methods, and cell lines and chromosomes produced by the methods. Methods for use of the artificial chromosomes are also provided.

Abstract: Transgenic animals and cells are provided that comprise an imaging marker transgene. The imaging marker is expressed on the cell surface, and is capable of binding at high affinity a radiolabeled hapten that provides a signal useful in emission computed tomography. A preferred imaging marker is an antibody fragment, e.g. a single chain variable region (scFv). Radiolabeled haptens of interest include metal chelates, and may also include radiolabled small molecules. The animals or cells are monitored in vivo by administering the radiolabeled hapten, and localizing expression through SPECT or PET acquisition and reconstruction.

Abstract: The c-Jun NH2-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal response to seizure activity. Methods of screening for molecules and compounds that decrease JNK3 expression or activity are described. Such molecules or compounds are useful for treating disorders involving excitotoxicity such as seizure disorders, Alzheimer's disease, Huntington disease, Parkinson's disease, and ischaemia.

Abstract: The present invention includes a basic method for discovering the function of gene and their corresponding gene products relative to a specific biological process or physiological condition. The invention provides the ability to develop therapeutic and diagnostic agents using the information obtained from the practice of the basic method. In the method, the gene product of a selected polynucleotide is delivered to a mammal to provide an immune response. The polynucleotide sequences may express, in vivo by immunization of an animal, or in bacterial system or other known system for expression of a polynucleotide sequence. The sera resulting from immunization with the gene product contains antibodies to the gene product which are used in function determinative assays to determine the function of the gene sequence gene product relative to a biological process or physiological condition, typically a disease in a human.

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: 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 method for raising antibodies in a mammalian host using live cells transfected with a biological of interest.

Abstract: Substantially human antisera are provided by genetically modifying a domestic animal generally weighing at least about 1 kg. The domestic animal is genetically modified by generating inactive heavy and light chain immunoglobulin loci and integrating at least functional portions of the human heavy and light chain immunoglobulin loci, whereby the human loci generate an immune response. The antisera find use in the treatment of diseases, immunocompromised patients and in case of transplantation.

Abstract: A microbial adherence inhibitor in the form of fowl egg antibodies is disclosed, along with the method of making it and methods of using it. The inhibitor functions by substantially preventing the attachment or adherence of colony-forming immunogens in the rumen and intestinal tracts of host food animals. The inhibitor is made by inoculating female birds with the immunogen, harvesting the eggs which contain antibodies to the immunogen, harvesting the eggs which contain antibodies to the immunogen, drying the egg contents and adding to the feed or water for the host animals.

Abstract: The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

Abstract: The invention is a performance-enhancing feed supplement. The feed supplement is made up of a combination of spray-dried porcine plasma and spray-dried hyperimmune egg. The feed supplement is effectively administered to increase performance when weanling pigs and calves.

Abstract: The present invention provides means and methods for obtaining an antibody in a mammary secretion product of a farm-animal comprising administering to said animal at least two compositions, which may be the same or different, comprising an antigen to which said antibody is to be raised, the method comprising administering at least a first of said compositions such that a high mucosal and/or systemic immune response is obtained and wherein at least a second of said compositions is administered to a mammary gland and/or a supramammary lymph node of said animal.

Abstract: The present invention relates generally to novel methods of producing transgenic chickens that generate antibodies or immunoglobulin polypeptides in whites of eggs. More specifically, one embodiment of the present invention relates to methods of inserting immunoglobulin-encoding transgenes into avian sperm cells for transfer to ova to generate transgenic zygotes. The transgenes may include at least two immunoglobulin-encoding nucleic acid sequences and an internal ribosome entry site (IRES) that allow the immunoglobulin polypeptides to be expressed by chicken cells and hence in egg whites.

Abstract: Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and/or advancement of the diseases.

Abstract: In humans, approximately 60% of expressed immunoglobulin light chains are of the Kappa type and 40% of the Lambda type. In mice, there is almost no expression from the Lambda locus and over 95% of light chains are of Kappa type. The present invention discloses, among other things, transgenic mice carrying most of the human Ig Lambda light chain locus in their genome. The resulting mice express light chains with Kappa/Lambda ratio similar to the human ratio. Breeding of HuIg Lamda mice to Kappa-deficient mice also is described, as well as the generation of human monoclonal antibodies from transgenic mice with human Ig Lambda locus.