Abstract: Genetically-modified mammals and immune cells are provided which are capable of producing or secreting detectably-labeled immunoglobulin molecules as a result of genetic modifications of at least one immunoglobulin gene in the genome thereof, such that a fusion polynucleotide encoding a detectable protein or peptide and an immunoglobulin component molecule is present.

Abstract: An anti-IL-23p19 antibody, including isolated nucleic acids that encode at least one anti-IL-23p19 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

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: Fully human antibodies 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: The present invention provides HEH4 polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing HEH4 polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with HEH4 polypeptides.

Abstract: The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

Abstract: Peptide antigens corresponding to amino acid residues 2-12, 1-12, 2-15 and 1-15 of parathyroid hormone (PTH), antibodies having an affinity to such peptide antigens and methods of producing the same. Such antigens, antibodies and methods producing the same according to the present invention are useful in determining bioactive intact PTH levels in serum, plasma, and/or cell culture media. Such antibodies further possess a high degree of species cross-reactivity, but substantially mitigated cross-reactivity to non-whole PTH peptide fragments and little to no recognition of the first amino acid residue of PTH.

Abstract: The present invention relates to recombinant human or humanized polypeptides which bind to ?5?1 integrin with high affinity and blocking function. Further, diagnostic and pharmaceutic applications of the potypeptides are disclosed.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: The present invention provides influenza A viruses that include a hemagglutinin subtype H2, a neuraminidase subtype N3, or the combination thereof. Included in the present invention are H2 hemagglutinins and N3 neuraminidases, and the polynucleotides encoding the polypeptides. Antibody to the polypeptides, and methods of using the viruses, polypeptides, polynucleotides, and antibodies are also provided.

Abstract: Monoclonal antibodies immunospecific for osteopontin are disclosed. Also provided are therapeutic methods of use thereof for modulating osteopontin levels for the treatment of autoimmune disorders.

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: The invention provides a product which comprises a C4bp core protein and a monomeric antigen, desirably in the form of a fusion protein. Monomeric antigens include malarial and influenza antigens. The C4bp core protein provides for assembly of multimeric complexes of the monomeric antigen, or mixtures thereof. The complexes are useful as vaccines.

Abstract: A method for efficiently generating antibodies immunizes an animal with a target antigen and a B cell expansion agent, such as an anti-CD40 agonist. The antibodies generated from this method are useful as therapeutic agents, diagnostic agents or research reagents in a variety of diseases and conditions.

Abstract: An improved method for producing human antibodies in SCID mice is provided. The improvement includes the use of dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents.

Abstract: The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

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 present invention relates to a caspase-8 interacting polypeptide (Cari), methods for its preparation, and its use.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV S protein, and that function to neutralize SARS-CoV. The invention also relates to antibodies that are bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-SARS-CoV S protein antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-SARS-CoV S protein antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.

Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and V?) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucelotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

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: 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 current invention relates to genetically engineered mice, cells derived from those mice, and polynucleotides and polypeptides corresponding to genes affected by the engineered mutation. The invention also relates to antibodies raised in a mouse of the invention. The invention further provides methods for using the mice, cells, polynucleotides, polypeptides and antibodies of the invention.

Abstract: The invention provides anovel approach for the suppression of endogenous antibody expression in non-human transgenic animals genetically engineered to express one or several human or humanized immunoglobulin transloci. Endogenous immunoglobulin expression in transgenic non-human animals is suppressed by selective expression of a suicide gene like a toxin only in B-cells expressing endogenous immunoglobulin but not in B-cells expressing human(ized) immunoglobulins. This method allows the dominant expression of transloci coding for humanized or human antibodies in the blood, milk and eggs of transgenic animals.

Abstract: The present invention relates to prevention and treatment of Alzheimer's disease (AD). More specifically, the invention relates to use of a non-wild type protofibril or compound(s) with protofibril forming activity for active immunisation in the purpose of treating or preventing AD. The invention further relates to a peptide, A?-Arc, with high protofibril forming activity as well as several applications thereof, such as antibodies against said peptide for passive immunisation against AD.

Abstract: A transmissible spongiform encephalopathy (TSE) agent is inactivated by exposing the TSE agent to a thermostable proteolytic enzyme at elevated temperature and at acid or alkaline pH. Following this step, or separately, presence of TSE infectivity is detected by detection of dimers of prion protein.

Abstract: Genetically engineered cells and animals are described that incorporate a mutated GHP1 allele. Animals that are homozygous for the mutated GHP1 allele are useful for the production of monoclonal antibodies against GHP1.

Abstract: The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody ? light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the nonhuman animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.

Abstract: The present invention relates to a method for generating anti-idiotypic antibodies comprising a) creating a non-human animal transgenic for an exogenous antibody, b) inducing an immune response in said transgenic non-human animal against an antibody of interest, whereby the antibody of interest comprises the same species-specific isotype as the exogenous antibody, and c) generating antibodies directed against the idiotypic part of the antibody of interest.

Abstract: The present invention aims at providing a high affinity anti-HIV antibody. According to the present invention, there are provided an antibody or a fragment thereof that binds to the gp12 glycoprotein of HIV and has a dissociation constant (KD) value of 1.

Abstract: Membrane proteins that are background antigens were solubilized, and transgenic animals were produced using genes encoding these soluble proteins. Antibodies against the background antigen membrane proteins comprised in the immunogens were not found in these transgenic animals, and even when genes encoding soluble proteins were used, immunotolerance against the full-length membrane proteins could be induced. Moreover, by expressing the background antigen membrane proteins as soluble proteins inside the bodies of transgenic animals, unfavorable phenotypes that appear when the full-length membrane proteins are expressed could be avoided, and such animals were made widely available as immunized animals.

Abstract: The invention relates to compounds which contain an antigen binding region which is bound to at least one enzyme which is able to metabolize a compound (prodrug) which has little or no cytotoxicity to a cytotoxic compound (drug), where the antigen binding region is composed of a single polypeptide chain. It is advantageous for covalently bonded carbohydrates to be present on the polypeptide chain.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

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: This invention provides novel methods of obtaining autologous monoclonal antibodies (AMABs) to self-antigens or homologs thereof. The method involves obtaining a genetically engineered host animal that does not biosynthesize at least one epitope of the antigen and utilizes the lack of self-tolerance of the host to the epitope to produce antibodies specific to the antigen. The invention also encompasses the AMABs produced by the methods. The invention further encompasses methods of isolating cells comprising the use of such AMABs that have specificity for a cell surface antigen.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucelotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.

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: The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.

Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and V?) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.

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: Antibodies and molecules derived therefrom that bind to novel STEAP-1 protein, and variants thereof, are described wherein STEAP-1 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, STEAP-1 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The STEAP-1 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 STEAP-1 can be used in active or passive immunization.

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production.

Abstract: The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Abstract: The present invention provides a method of making an isolated human monoclonal antibody, said antibody binds a mitochondrial antigen bound by a human autoantibody found in patients with PBC. Said method involves using a transgenic non-human animal that has the ability to make human antibodies.

Abstract: The invention provides a novel approach for suppression of endogenous antibody expression in non-human transgenic animals genetically engineered to express one or several human or humanized immunoglobulin transloci. Polyclonal or one or several monoclonal antibodies specific for endogenous IgM and/or IgE heavy and/or light chains are administered to the transgenic animals such that B-cells expressing their endogenous immunoglobulin are depleted and consequently expression of endogenous immunoglobulin is suppressed. Alternatively endogenous immunoglobulin expression may be inhibited through the expression of transgenes encoding such antibodies, including antibody fragments. This method allows the dominant expression of transloci coding for humanized or human antibodies in the blood, milk and eggs of transgenic animals.

Abstract: The invention relates to a transgenic non-human animal cell characterized in that it expresses at least one nucleotide sequence coding for at least one of the chains of human receptors of the fragment Fc of IgE immunoglobulins (Fc&egr;R)) and a nucleotide sequence coding fo a human origin, characterized in that the murine gene coding for the chain Fc&egr;)R) of the human receptor is inactive. The invention also relates to a corresponding transgenic animal and a method for understanding physiopathological elements involved in immediate hypersensitivity and/or inflammatory mechanisms. The invention further relates to a method for screening active compounds on interactions between human IgE's and the receptors thereof.

Abstract: The invention provides methods for fusing a first cell with a second cell to form a hybrid cell. The methods involve incubating a first parental cell producing a first partner of a fusogenic binding partner pair on its surface with a second parental cell producing a second partner of the fusogenic binding partner pair on its surface. In certain embodiments, the parental cells are incubated with a known fusogen such as polyethylene glycol and the fusogenic binding partner pair increases the rate of cell fusion. In many embodiments, the first cell is an antibody producing cell, the second cell is an immortal cell, and the hybrid cell is a hybridoma cell that produces a monoclonal antibody. Also provided by the invention are methods for producing hybridoma cells, and methods for screening those cells for production of a monoclonal antibody of interest. The invention further provides systems and kits for carrying out the subject methods.