Abstract: The invention relates to the production of proteins and other substances of interest in saliva of transgenic animals, particularly in mammals that produce large quantities of saliva, particularly monogastric ruminants, and ovine, caprine and bovine mammals. Preferred embodiments of the invention relate in particular to the production of foreign and modified proteins in the transgenic saliva of these animals, including particularly human fibrinogen, human prothrombin and human thrombin, among others. The invention relates as well to methods, devices, genetic constructs and to transgenic constructs for making the proteins and other substances of interest, to novel saliva and saliva-derived compositions, novel products from the saliva, and to uses of the saliva, saliva-derived compositions and novel products.

Abstract: The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions. The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

Abstract: A transgenic silkworm system for recombinant glycoprotein production is provided.

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: Individual monoclonal antibodies and fragments that bind a conserved epitope of the G protein of RSV and which are minimally immunogenic when administered to a human subject, are useful in treating RSV infections.

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: A non-human transgenic mammalian animal, as described above, contains one or more exogenous double stranded DNA sequence(s) stably integrated into the genome of the animal, which comprises trans-acting regulatory units controlling expression of DNA sequences encoding proteins to be secreted into the milk of transgenic mammals. The DNA sequence of the trans-regulatory gene encodes transcriptional activating proteins, which are not secreted but made in a temporally controlled and mammary tissue specific manner. The DNA sequence containing the protein to be secreted in the milk is constructed on a separate gene sequence under the regulation of a minimal promoter and a trans-activation binding domain. The transgenic mammals are preferably pigs, cows, sheep, goats and rabbits. A related composition and method for making transgenic proteins which require specialized propeptides for proper post-translational processing is also described.

Abstract: The invention relates to mice having functionally silenced endogenous lambda (?) and kappa (?) L-chain loci, comprising antibody-producing cells in which the CH1 domain is functionally silenced, either via spontaneous processes in somatic antibody-producing cells or due to germline deletion of the CH1 domain. Mice of the invention are capable of producing H-chain-only antibody lacking a functional CH1 domain; transgenic human heavy-chain-only antibodies lacking a functional CH1 domain can be produced following insertion into the mouse of an artificial locus with human heavy chain V, D and J segments and a constant region, which is preferably a modified constant region with alterations in, around or upstream of a CH1 domain and/or removal of a CH1 domain.

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: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.

Abstract: The invention includes methods of making transgenic avians by introducing a nucleic acid sequence into the genome of an avian embryo wherein the nucleic acid sequence comprises a nucleotide sequence encoding a heterologous protein, developing the avian embryo to hatch, developing the hatched chick to sexual maturity and obtaining offspring from the sexually mature hatched chick which produce egg white containing the heterologous protein.

Abstract: The present invention relates to at least one novel human anti-amyloid antibody, including isolated nucleic acids that encode at least one anti-amyloid antibody, amyloid, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.

Abstract: The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to chondroitin sulfate, particularly CS-A, CS-C and CS-E tetrasaccharides. The present invention also relates to methods of making anti-CS antibodies, pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for diagnosis and treatment.

Abstract: Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland.

Abstract: The present invention provides a method for producing a transgenic (Tg) non-human animal capable of developing an enhanced humoral immune response against an antigen as compared to a non-transgenic control animal of the same species, comprising introducing into said non-human animal a genetic construct providing for enhanced MHC class I-related neonatal Fc receptor (FcRn) activity. Also provided a Tg non-human animal comprising a genetic construct providing for enhanced FcRn activity, as well as the use of such animal in a non-therapeutical method. Therapeutic genetic constructs and methods are also provided. The present invention further provides methods for producing immunoglobulins.

Abstract: A transgenic animal such as a transgenic snake or other reptile that expresses a heterologous expression product is described, along with methods of making the same. In general, the animal comprises cells containing a sequence encoding the heterologous expression product. The sequence encoding the heterologous expression product is integrated into the genome of the animal (e.g., in some or all cells thereof, and in some embodiments into germ cells thereof). The sequence encoding the heterologous expression product is, in general, operatively associated with an expression sequence or promoter. The animals are useful for, among other things, testing of repellents, testing of toxicological compounds, as teaching aids, for venom production, etc.

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 a genetic engineering material for insects that enables a target protein to be purified easily, without requiring the use of recombinant baculovirus, while simultaneously providing a process for producing exogenous protein using that genetic engineering material. A gene recombinant silkworm is obtained by inserting an exogenous protein gene such as a cytokine gene coupled to a promoter that functions in silk glands into a silkworm chromosome. An exogenous protein such as a cytokine is then extracted and purified from the silk glands or cocoon of that silkworm or its offspring. A large amount of exogenous protein can be produced within silk gland cells, outside silk gland cells or in silk thread or a cocoon by inserting an expression gene cassette, in which the DNA sequence of the 3? terminal portion and the DNA sequence of the 5? terminal portion of fibroin H chain gene are fused to the exogenous protein gene, into silk gland cells and so forth.

Abstract: The invention includes methods of producing proteins in transgenic avians containing nucleic acids in their genome which contain an exogenous lysozyme gene expression controlling nucleotide sequence which typically is linked to a polynucleotide encoding a heterologous polypeptide.

Abstract: A transgenic insect cell line for production of recombinant glycoproteins possessing sulfated, complex N-glycans is provided.

Abstract: The present invention provides a polypeptide having a wide substrate specificity and having a ?3 fatty acid desaturation activity, which makes efficiently unsaturated bond at ?3 position, and a polynucleotide coding for the same. By expressing the polypeptide in the organism, mass production of n-3 series PUFAs is enabled. Specifically, the polypeptide having a ?3 fatty acid desaturation activity and consisting of the amino acid sequence represented by SEQ ID NO: 1, a polynucleotide coding for a polypeptide having a ?3 fatty acid desaturation activity that consists of the base sequence represented by SEQ ID NO: 2 or SEQ ID NO: 3, and the like is useful for production of n-3 series fatty acids.

Abstract: Isolated anti-IL-12 antibodies, nucleic acids encoding antibodies or antibody portions, vectors, host cells, and methods of making are useful for production of antibody or portions for treating and/or diagnosing IL-12 related conditions, diseases, and disorders.

Abstract: Antibodies having dual specificity for two different but structurally related antigens are provided. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have dual specificity for IL-1? and IL-1? and neutralize IL-1? and IL-1? activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting two different but structurally related antigens (e.g., IL-1? and IL-1?) and for inhibiting the activity of the antigens, e.g., in a human subject suffering from a disorder in which IL-1? and/or IL-1? activity is detrimental.

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: 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 present invention relates to at least one novel anti-alpha-V subunit antibodies, including isolated nucleic acids that encode at least one anti-alpha-V subunit antibody, alpha-V subunit, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The invention includes delivering to an avian a nucleic acid molecule which includes nucleotide sequence of an ovalbumin gene expression controlling region and a heterologous coding sequence operably linked to the gene expression controlling region wherein the heterologous coding sequence is expressed in a cell of the avian.

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 DNA molecule is provided which comprises a sequence according to SEQ ID NO: 1 having an open reading frame from base pair 211 to base pair 1740 or having at least 50% homology to the above-indicated sequence, or hybridizing with the above-indicated sequence under stringent conditions, or comprising a sequence which has degenerated to the above-indicated DNA sequence because of the genetic code, the sequence coding for a plant protein having fucosyltransferase activity or being complementary thereto.

Abstract: The present invention relates to at least one novel anti-alpha-V subunit antibodies, including isolated nucleic acids that encode at least one anti-alpha-V subunit antibody, alpha-V subunit, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: Methods for generating antibodies in rodents are disclosed. The antibodies are useful as therapeutic agents, diagnostic agents or research reagents.

Abstract: The invention includes methods of producing viral particles which include introducing into avian cells a nucleotide sequence encoding a replication deficient retroviral vector and introducing into the avian cells nucleotide sequence encoding products required for replication of the replication deficient retroviral vector, harvesting the viral particles and can include administering the viral particles to vertebrate cells.

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: This invention provides: a pluripotent cell derived from a non-human animal comprising foreign DNA that encodes a desired protein in such a manner that the expression of the desired protein is regulated by the control region of a gene expressed in certain cells and/or tissue, wherein the foreign DNA is bound to a nucleic acid fragment comprising a promoter/the whole or part of 5? non-translational region/a leader sequence coding region derived from a gene expressed in certain cells and/or tissue, and wherein in said cell one or more drug resistant marker genes used for introducing the foreign DNA into the genome have been removed; a chimeric non-human animal that is prepared from the pluripotent cell and highly expresses the desired protein, or a progeny thereof; a method for producing a desired protein using the chimeric animal; and a method for analyzing in vivo function of a desired gene using the chimeric animal.

Abstract: The present invention is directed to a vector and its use to generate genetically modified animals and cells. One aspect of this invention involves a vector that comprises a sperm cell and one or more polynucleotide molecules bound to a sperm cell through one or more sperm antibody linker. The sperm cell can be any animal sperm cell, preferably non-human animal such as a mouse, pig, sheep, goat, or chicken. In one preferred embodiment of this invention, the one or more polynucleotide molecules encode for a gene product that confers desired characteristics in the cells or the animals. In another preferred embodiment of this invention, the genetically modified cells are able to produce desired therapeutic proteins. The association of the sperm, linker, and the one or more polynucleotide can also occur in vitro or in vivo. In another embodiment, the genetically modified cells are transgenic chicken eggs in which one or more desired recombinant protein is expressed.

Abstract: An improved method for recovering recombinantly produced polypeptides is described. The method involves expressing the recombinant polypeptide as a fusion protein with a pro-peptide. The pro-peptide-polypeptide fusion protein can be cleaved and the recombinant polypeptide released under the appropriate conditions.

Abstract: This invention provides eggs which contain exogenous proteins. The invention further provides transgenic chickens which express exogenous sequences in their oviducts, and vectors and methods for the stable introduction of exogenous nucleic acid sequences into the genome of a bird for expressing said exogenous sequences to alter the phenotype of the bird or to produce desired proteins.

Abstract: The present invention relates to a novel method for preparing gamma-carboxylated poly-peptides, including coagulation Factors VII, IX, X and Protein C. The present invention also relates to novel host cells and recombinant vectors to be used in this improved method for preparing gamma-carboxylated polypeptides.

Abstract: Erythropoietin obtained from eggs laid by transgenic avians having avian N-linked and O-linked glycosylation patterns.

Abstract: An improved method for recovering recombinantly produced polypeptides is described. The method involves expressing the recombinant polypeptide as a fusion protein with a pro-peptide. The pro-peptide-polypeptide fusion protein can be cleaved and the recombinant polypeptide released under the appropriate conditions.

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: The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig? and/or Ig? sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig? and/or Ig? sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig? and/or Ig? results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Abstract: Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-? (TNF?) and are useful in vivo diagnosis and therapy of a number of TNF?-mediated pathologies and conditions, including ankylosing spondylitis, as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided.

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.

Abstract: As novel means for causing any recombinant protein produced by the silkworm middle silk gland to be secreted in cocoons and easily extracting the recombinant protein from the cocoons without modification of the conformation of the protein, there is provided a polynucleotide that in an expression cassette for expression of a recombinant protein by the silkworm middle silk gland, is functionally linked to a recombinant protein structure gene, which polynucleotide is one composed of a polynucleotide constructing the promoter regions of sericin 1 or sericin 2 gene and, functionally linked thereto, a polynucleotide constructing the homologous regions of baculovirus.

Abstract: Transgenic silkworms comprising GFP whose expression is regulated by the sericin gene promoter were produced. Observation of the silk glands of the last instar larvae of the silkworms showed fluorescence only in the middle silk glands. GFP was secreted from middle silkgland cells from around the spinning stage, indicating that GFP moved into the gland lumen. Finally, GFP was spun into cocoon filaments, and cocoons containing large amounts of GFP were produced. Thus, by using the promoter region of the sericin gene, recombinant proteins can be produced in the middle silk glands. Furthermore, the recombinant proteins produced in the middle silk glands were readily secreted into the lumen of the middle silk glands.

Abstract: Mass spectrometry-based methods are described for the detection or quantification of targeted proteins in biological samples e.g., plants, animals, and microorganisms, parts (e.g., tissue or cells) thereof, and products derived from plants, animals or microorganisms.

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

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.