Abstract: The present invention relates to new compositions for the oral administration of apolipoproteins in the dimeric or multimeric form, with specific dosage regimens for use in the treatment of atherosclerosis.

Abstract: Methods of making recombinant secretion of silk and silk-amyloid proteins using bacteria are provided.

Abstract: The present invention relates to a method for the production of novel T-cell receptors (TCR) which provide a reduced risk of adverse events in immune therapy, specifically in adoptive T cell transfer. The TCRs produced according to the method of the invention are specific for tumor cells and do not react with healthy tissue. Furthermore provided are nucleic acids encoding the TCR of the invention, vectors and host cells comprising the TCRs of the invention as well as their use is the treatment of tumorous diseases.

Abstract: The present disclosure provides antibodies that bind the surface of Toxoplasma gondii oocysts, methods for using such antibodies and kits and devices for practicing such methods. Such antibodies, methods, kits and devices find use in detection of T. gondii oocysts and the isolation of such oocysts from samples including environmental samples, food-based samples, diagnostic samples, and the like.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.

Abstract: The present invention relates generally to the field of immunology. More particularly, aspects of the invention concern the discovery of several T cell receptors (TCRs) that are specific for an immunodominant CTL epitope of hepatitis C virus (HCV). Embodiments include TCRs, DNAs encoding TCRs, methods of making TCRs, and methods of using TCRs to treat, prevent or inhibit hepatitis C virus (HCV) proliferation.

Abstract: The present invention relates to a nucleic acid for vaccine that has undergone codon optimization for expression in Bombyx mori, a vector comprising the nucleic acid, Bombyx mori comprising the vector, and a method for producing a vaccine in which they are used.

Abstract: The invention relates to polynucleotides, particularly chimeric polynucleotides useful for optimal production of functional immunoglobulins with human idiotypes in rodents. The invention further relates to rodents comprising such polynucleotides.

Abstract: Transgenes encoding exogenous antibodies are stably integrated into donor cells and are present in the somatic tissue of chimeric birds. The transgenes encode exogenous antibodies and are preferably expressed in the oviduct for collection in the egg. Tissue specificity is provided by selecting the content of the transgene accordingly. Birds whose genome is comprised of transgene-derived exogenous antibody-encoding DNA express exogenous antibodies having desirable chemical properties with increased therapeutic utility compared to antibodies derived from bacterial expression systems.

Abstract: The invention relates to transgenic birds capable of producing chimeric immunoglobulins, with a combination of human and avian sequence, in their B cells. In some embodiments, the birds are chickens. When challenged with an antigen, the transgenic avians produce antigen-specific functional antibodies. The invention also relates to light chain immunoglobulin transgenes for making such transgenic avians, as well as methods and vectors for disrupting endogenous immunoglobulin loci in birds.

Abstract: Pentameric CRP is produced at a high efficiency by transferring DNA, which encodes monomeric CRP, into a silkworm to thereby construct a transgenic silkworm and then collecting and purifying pentameric CRP that is produced by the transgenic silkworm constructed above.

Abstract: A transgenic avian containing in its genome an exogenous nucleotide sequence which includes a promoter component and a vector with reduced promoter interference wherein the exogenous nucleotide sequence is integrated into the genome and the avian.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.

Abstract: An aim is to produce a suitable foreign protein in egg white in transgenic birds at levels equivalent to or higher than the expression levels achieved using an ovalbumin promoter or an actin promoter, and to reduce the great burden on birds by reducing the expression at sites other than the oviduct while achieving expression sufficient to predict the expression levels before the birds reach sexual maturity. Provided is a transgenic bird containing a nucleic acid base sequence in chromosome in a cell that forms the oviduct, the sequence containing: (a) an avian endoplasmic reticulum chaperone promoter; and (b) a nucleic acid base sequence encoding a suitable foreign protein, functionally linked to the promoter. Also provided is a method for producing a suitable foreign protein, including recovering the suitable foreign protein from the transgenic bird.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: This invention relates to the biotechnology area, and provides a kind of TRAIL chimeric protein, DNA sequence encoding this chimeric protein, vectors comprising this DNA, host cells or transgenic animals that contain one of the vectors, and preparation methods for the said chimeric protein and its applications. The said TRAIL fusion protein from the N to C terminal comprises human leucine zipper sequence, human TRAIL protein, human TRAIL extracellular domain or a fragment thereof. The chimeric protein has significantly enhanced stability, prolonged half-life in animals, increased efficacy and thus has broad application future.

Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: The invention relates to a non-human transgenic mammal with an IgH locus modified by replacement of the switching sequence S? with all or part of a transgene comprising the gene C? of a class A human immunoglobulin, including at least the exon, coding for the CH3 domain and the membrane exon and the applications of the above for the production of humanized class IgA antibodies.

Abstract: The present invention provides, inter alia, transgenic non-human animals, such as transgenic mice. The animals contain in their genome a polynucleotide encoding a von Willebrand factor (VWF) polypeptide, which polypeptide forms a thrombus when in the presence of human platelets. Nucleic acid sequences and vectors for generating the transgenic non-human animals, and methods for using the transgenic non-human animals are provided as well. Chimeric VWF proteins are also provided.

Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: The invention includes isolating pharmaceutical proteins from avian hard shell eggs containing pharmaceutical proteins wherein the pharmaceutical proteins are exogenous to the egg.

Abstract: The present invention provides a novel fusion polypeptide containing a catalytic portion of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

Abstract: A transgenic avian containing in its genome an exogenous nucleotide sequence which includes a promoter component and a vector with reduced promoter interference wherein the exogenous nucleotide sequence is integrated into the genome and the avian.

Abstract: The present invention describes mRNA usage improving and/or translation-enhancing nucleic acid sequences, nucleic acid constructs comprising such sequences, and host cells comprising such nucleic acid constructs. The invention further pertains to a method for expressing a protein of interest in a cell or organism using such nucleic acid sequences, as well as their uses for increasing integration of such nucleic acid construct into a genome, for enhancing mRNA usage and/or translation of a recombinantly expressed polypeptide, and for increasing the number of transformants upon transformation of a cell with such nucleic acid construct.

Abstract: This invention provides for proteins which are expressed in the avian oviduct, packaged into eggs laid by the avian, then isolated.

Abstract: Disclosed are a protein encoded by any one of nucleic acids (i) to (iv): (i) a nucleic acid having a base sequence of SEQ ID NO: 1; (ii) a nucleic acid encoding a protein having an amino acid sequence of SEQ ID NO: 2; (iii) a nucleic acid encoding a dragline protein and having a sequence identity of 90% or more with the nucleic acid (i); (iv) a nucleic acid which encodes a dragline protein and hybridizes with a complementary chain of the nucleic acid (i) under stringent conditions, and a silk thread containing the protein.

Abstract: The invention provides methods for isolating cell-type specific mRNAs by selectively isolating ribosomes or proteins that bind mRNA in a cell type specific manner, and, thereby, the mRNA hound to the ribosomes or proteins that bind mRNA. Ribosomes, which are riboprotein complexes, bind mRNA that is being actively translated in cells. According to the methods of the invention, cells are engineered to express a molecularly tagged ribosomal protein or protein that binds mRNA by introducing into the cell a nucleic acid comprising a nucleotide sequence encoding a ribosomal protein or protein that binds mRNA fused to a nucleotide sequence encoding a peptide tag. The tagged ribosome or mRNA binding protein can then be isolated, along with the mRNA bound to the tagged ribosome or mRNA binding protein, and the mRNA isolated and further used for gene expression analysis.

Abstract: Pentameric CRP is produced at a high efficiency by transferring DNA, which encodes monomeric CRP, into a silkworm to thereby construct a transgenic silkworm and then collecting and purifying pentameric CRP that is produced by the transgenic silkworm constructed above.

Abstract: Transgenic silkworms comprising at least one nucleic acid encoding a chimeric silk polypeptide comprising one or more spider silk elasticity and strength motifs are disclosed. Expression cassettes comprising nucleic acids encoding a variety of chimeric spider silk polypeptides (Spider 2, Spider 4, Spider 6, Spider 8) are also disclosed. A piggyBac vector system is used to incorporate nucleic acids encoding chimeric spider silk polypeptides into the mutant silkworms to generate stable transgenic silkworms. Chimeric silk fibers having improved tensile strength and elasticity characteristics compared to native silkworm silk fibers are also provided. The transgenic silkworms greatly facilitate the commercial production of chimeric silk fibers suitable for use in a wide variety of medical and industrial applications.

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: This invention provides vectors and methods for the stable introduction of exogenous nucleic acid sequences into the genome of a bird and for expressing said exogenous sequences to alter the phenotype of the bird or to produce desired proteins. In particular, transgenic chickens are produced which express exogenous sequences in their oviducts. Eggs which contain exogenous proteins are also produced.

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 present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support.

Abstract: Transgenic rodents having NGF beta gene mutants in their genomes express NGF beta mutant proteins. The preparation methods of the transgenic rodents, the methods of utilizing the transgenic animals to prepare NGF beta mutant proteins and the resulting NGF beta mutant proteins are provided. The transgenic rodents are useful in preparing human NGF and in the study of the functions of NGF beta mutants and their receptors in the whole animal level, and also useful for screening and purifying NGF beta mutants which have high activity and high security.

Abstract: Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

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: Transgenic avians which produce proteins in their oviduct tissue having modified oligosaccharide structures and methods of making such avians are disclosed herein. The invention also includes the modified proteins produced in the transgenic birds.

Abstract: Silkworms which have (i) a DNA encoding a transcriptional regulator operably linked downstream of a promoter of a DNA encoding a protein specifically expressed in the silk gland and (ii) a DNA encoding TRACP5 operably linked downstream of a target promoter of the transcriptional regulator were produced. The result showed that active TRACP5b was produced from the silkworms. This means that TRACP5 produced from the silk gland of the silkworms undergoes processing in the silk gland that is similar to the processing taking place at bone resorption sites.

Abstract: The present invention provides compositions comprising an isolated mixture of recombinant human NaGlu proteins in which a substantial amount of the NaGlu proteins in the mixture has increased levels of phosphorylated mannose that confer the proteins to be efficiently internalized into human cells. The present invention also provides methods of producing such mixture of NaGlu proteins, vectors used in transgenesis and expression, host cells harboring such vectors, and methods of isolating and purifying the mixture of NaGlu proteins. The invention further provides methods of treating NaGlu associated diseases.

Abstract: The present invention relates to a recombinant organism having any one of nucleic acids (i) to (iv) introduced therein: (i) a nucleic acid having a base sequence of SEQ ID NO: 1; (ii) a nucleic acid encoding a protein having an amino acid sequence of SEQ ID NO: 2; (iii) a nucleic acid encoding a dragline protein and having a sequence identity of 90% or more with the nucleic acid (i); (iv) a nucleic acid which encodes a dragline protein and hybridizes with a complementary chain of the nucleic acid (i) under stringent conditions.

Abstract: The present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support.

Abstract: Transgenes encoding exogenous antibodies are stably integrated into donor cells and are present in the somatic tissue of chimeric birds. The transgenes encode exogenous antibodies and are preferably expressed in the oviduct for collection in the egg. Tissue specificity is provided by selecting the content of the transgene accordingly. Birds whose genome is comprised of trangene-derived exogenous antibody-encoding DNA express exogenous antibodies having desirable chemical properties with increased therapeutic utility compared to antibodies derived from bacterial expression systems.

Abstract: The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to CD40, preferably human CD40, and that function as CD40 agonists. The invention also relates to human anti-CD40 antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, 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-CD40 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-CD40 antibodies, compositions comprising these antibodies and 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-CD40 antibodies.

Abstract: The present invention relates to anti-TNF antibodies comprising all of the heavy chain variable CDR regions of SEQ ID NOS:1, 2 and 3 and/or all of the light chain variable CDR regions of SEQ ID NOS:4, 5 and 6, specific for at least one human tumor necrosis factor alpha (TNF) protein or fragment thereof, as well as nucleic acids encoding such anti-TNF antibodies, complementary nucleic acids, vectors, host cells, production methods and therapeutic methods.

Abstract: The invention provides transgene constructs for expressing chimeric antibodies, and transgenic non-human host animals carrying such constructs, wherein the chimeric antibodies comprise human variable regions and constant regions of the non-human transgenic host animal. The presence of immunoglobulin constant regions of the host animal allows for generation of improved antibodies in such transgenic host animals. Subsequently, the chimeric antibodies can be readily converted to fully human antibodies using recombinant DNA techniques. Thus, the invention provides compositions and methods for generating human antibodies in which chimeric antibodies raised in vivo in transgenic mice are used as intermediates and then converted to fully human antibodies in vitro.

Abstract: Disclosed is a mouse artificial chromosome vector, comprising: a natural centromere derived from a mouse chromosome; a mouse-chromosome-derived long-arm fragment formed by deleting a long-arm distal region at a mouse chromosome long-arm site proximal to the centromere; and a telomere sequence, wherein the vector is stably retained in a cell and/or tissue of a mammal. In addition, disclosed are cells or non-human animals comprising the vector, and use of the cells or non-human animals.

Abstract: Methods and compositions for the administration of transposon-based vectors to the reproductive organs of animals and the creation of transgenic animals. Preferred methods involve administration of the transposon-based vectors to the lumen of the oviduct of an avian, expression of a vector derived transgene in the avian, and deposition of the resultant polypeptide in an egg. This invention allows for large amounts of protein to be deposited in the egg.

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: A method for the detection and isolation of ligands, preferably nuclear receptor ligands, bound to their cognate receptors in live animals, is described. A novel composition comprising 1) a chimeric transcription factor containing a DNA-binding domain, preferably from a non-vertebrate transcription factor, fused to the ligand-binding domain (LBD) of a nuclear receptor, 2) a reporter system, driven by a promoter that contains binding sites for the chosen DNA-binding domain, 3) multiple affinity tags fused to the LBD fusion proteins to facilitate efficient purification, along with specifically associated molecules and 4) sequences required for simultaneous genomic integration of all three components above are described. To make use of the system, expression of the chimeric LBD protein is broadly induced.