Abstract: Reconstituted human breast tumor models are disclosed. The models, which are incorporated into mice, provide actual tumors that arise spontaneously, thereby mimicking naturally occurring breast cancer. The tumors are genetically human, because they arise from human mammary tissues that develop from human mammary epithelial cells implanted into host mice. Prior to implantation, the mammary epithelial cells are genetically modified to contain either: (a) a recombinant human oncogene and an SV40er; or (b) a recombinant human oncogene, a transgene or shRNA that inhibits the p53 pathway, and a transgene or shRNA that inhibits the Rb pathway.

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: It is intended to provide a simple normal-tension glaucoma model capable of spontaneously, age-dependently and surly developing conditions similar to symptoms of normal-tension glaucoma which occurs more frequently in elder people, and a method of evaluating therapeutic effect on normal-tension glaucoma whereby a drug useful in treating and diagnosing can be conveniently screened by using the normal-tension glaucoma model. A normal-tension glaucoma model comprising a nonhuman mammal, which is deficient in a transcriptional regulator NF-?Bp50 and thus spontaneously develops the normal-tension glaucoma symptom age-relatedly, an organ or a tissue thereof or cells collected from any of the same.

Abstract: The present invention relates to a novel isolated humanized antibody, or the derived compounds or functional fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and/or heterodimers. More particularly, the present invention relates to hz515H7 antibodies, specific to the CXCR4 protein, as well as their use for the treatment of cancer. Pharmaceutical compositions composed of such antibodies and a process for the selection of such antibodies are also covered.

Abstract: The present invention relates to the use of a milled homogenate and/or a suspension and/or a cell lysate, stemming from a tumor resistant to at least one anti-tumoral compound in order to immunize and generate in vitro an antibody, or one of its functional fragments, directed against a tumoral antigen specifically expressed at the surface of said resistant tumor and being possibly involved in the resistance of said resistant tumor. More particularly, the present invention is directed to such antibodies obtained by applying the method, such as the antibodies 1A6, 1A9, 2E11, 3C11 and 3G7, as well as to their use for treating cancer.

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: Genetically modified nematodes and methods for using the same are provided.

Abstract: The present invention provides new lentiviral vectors that include an anti-repressor element (ARE) and, optionally, a scaffold attachment region (SAR). The lentiviral vectors provide expression of a heterologous nucleic acid in at least 50% of the cells of multiple cell types when used for lentiviral transgenesis. In certain embodiments of the invention the heterologous nucleic acid encodes an RNAi agent such as an shRNA. The invention further provides transgenic nonhuman animals generated using a lentiviral vector that includes an ARE and optional SAR. In addition, the invention provides a variety of methods for using the vectors including for achieving gene silencing in eukaryotic cells and transgenic animals, and methods of treating disease. The invention also provides animal models of human disease in which one or more genes is functionally silenced using a lentiviral vector of the invention.

Abstract: Proteases derived from Nocardiopsis dassonvillei subsp. dassonvillei DSM 43235, Nocardiopsis prasina DSM 15649, Nocardiopsis prasina (previously alba) DSM 14010 Nocardiopsis sp. DSM 16424, Nocardiopsis alkaliphila DSM 44657 and Nocardiopsis lucentensis DSM 44048, as well as homologous proteases; their recombinant production in various hosts, including transgenic plants and non-human animals, and their use in animal feed and detergents. The proteases are acid-stable, alkali-stable, and/or thermostable.

Abstract: Recombinant protein constructs are described that comprises a membrane protein whose N- or C-terminus in the native state is recombinantly linked through a membrane-spanning linker polypeptide to a reporter polypeptide. The reporter polypeptide may be a fluorogen activating protein capable of binding a fluorogen to detect the location and relative abundance of the membrane protein, and more specifically to detect protein trafficking to the cell surface using a cell impermeant fluorogen probe.

Abstract: A monomer of an I-CreI meganuclease variant wherein said monomer when in dimeric form binds and cleaves DNA.

Abstract: The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12R?2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

Abstract: Compositions for nematode growth and methods for using the same for nematode viability are described. The compositions contain a solid matrix material that is dispersed in a liquid medium. The solid matrix can be immersed, bathed, and/or interspersed in a liquid medium to form a composite culture that is capable of maintaining or growing nematodes at unexpectedly high densities and/or with nominal stress pathway activity. Other embodiments are described.

Abstract: The use of interferon induced transmembrane protein 1, 2, or 3 (IFITM1, 2, or 3) as a viral restriction factor, and methods of using the same to produce virus, transgenic animals expressing exogenous IFITM1, 2, or 3, and methods of treating or inhibiting viral infections by targeting a gene identified herein

Abstract: Mutations of the epidermal growth factor receptor (EGFr), of phosphatidylinositol 3?-kinase (“PI3K”), and of B-Raf are described. Methods of treating tumors containing mutated EGFr with human monoclonal antibodies against EGFr are described. Methods and kits for ascertaining the presence of one or more mutant EGFr, mutant PI3K, and/or mutant B-Raf in a sample and for treating disorders or conditions related to the presence of mutant EGFr, mutant PI3K, and/or mutant B-Raf are also described. Methods of treating tumors containing mutant EGFr, mutant PI3K, and/or mutant B-Raf are also described.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to c-Met, preferably human c-Met, and that function to inhibit c-Met. The invention also relates to human anti-c-Met 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-c-Met antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-c-Met 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-c-Met antibodies.

Abstract: A monomer of an I-CreI meganuclease variant wherein said monomer when in dimeric form binds and cleaves DNA.

Abstract: The present invention refers to human EGLN2 variants having at position 58 of the amino acid sequence a serine or a leucine and their use in the prevention or treatment of thromboembolic or coronary heart diseases, in particular stroke, prolonged reversible ischemic neurological deficit (PRIND), transitoric ischemic attack (TIA), myocardial infarction and/or early myocardial infarction.

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 produced from the saliva, and to uses of the saliva, saliva-derived compositions and novel products.

Abstract: A genetically modified mouse characterized in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide.

Abstract: Laboratory-selected colonies of western corn rootworm exhibiting tolerance to maize containing event DAS-59122-7 are described. Further, methods for various uses of these resistance western corn rootworm colonies are also described, including development of negative cross-resistance strategies and improved resistance management strategies.

Abstract: A monomer of an I-CreI meganuclease variant wherein said monomer when in dimeric form binds and cleaves DNA.

Abstract: Systems and methods relate to transgenic organisms and their use as biosensors are described. In some embodiments, the systems and methods include a first population of transgenic organisms that includes a first constitutively expressed reporter gene, and a first transgene that includes a first inducible promoter from a response pathway gene, wherein the first inducible promoter is coupled to a first reporter gene. Other embodiments are described.

Abstract: Disclosed herein are an ?1/CaV3.1 double knockout mouse or ?1?/?; Emx1-Cre mouse with enhanced essential tremor and a screening method of therapeutic agents for essential tremor by using the same. The ?1/CaV3.1 double knockout mouse or ?1?/?; Emx1-Cre mouse of the present invention may be usefully used for development of therapeutic agents for essential tremor because the mouse exhibits essential tremor strong and evident enough to be visually confirmed, compared to an ?1 knockout mouse.

Abstract: It has been determined that most mutations in factor VIII occur in multiple haplotypes, not primarily in one haplo-type. The frequencies of mild, moderate, and severe hemophilia did not differ significantly according to the background haplo-type. The odds of having inhibitor were significantly higher among patients in the H3+H4 haplotype groups as compared to H1+H2 haplotype groups. This association appears to be independent of the mutation. The results indicate that white hemophiliacs should be treated with Kogenate®. However, it would clearly be of benefit to assess the haplotype of black hemophiliacs prior to prescribing the recombinant FVIII to be used for treatment. It is not essential to determine the actual mutations responsible for the hemophilia prior to prescribing the recombinant FVIII. Also described are transgenic human FVIII animal models.

Abstract: The present invention provides for a method of evaluating whether a compound is effective in activating a calcium-calmodulin dependent kinase II? promoter in a human neuronal cell which comprises: (a) contacting the human neuronal cell which has been stably transformed by a recombinant nucleic acid molecule comprising a gene of interest operatively linked to a nucleic acid encoding a calcium-calmodulin dependent kinase II? promoter which has a nucleotide sequence of the promoter in ATCC Accession No. 98582 with the compound, and (b) comparing the expression level of the gene of interest in the neuronal cell in step (a) with the level in the neuronal cell in the absence of the compound, thereby determining whether the compound is effective in activating the calcium-calmodulin dependent kinase II? promoter.

Abstract: The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter; and (b) a DNA sequence which encodes a receptor for advanced glycation endproducts (RAGE), wherein the promoter and the DNA sequence which encodes the receptor for advanced glycation endproducts (RAGE) are operatively linked to each other and integrated in the genome of the non-human animal, and wherein said non-human animal exhibits a reduced amount of cerebral tissue infarcted following a transient middle cerebral artery occlusion compared to an identical non-human animal lacking said DNA sequence.

Abstract: The present invention relates to new antibodies capable of binding specifically to the human CD151 protein, especially monoclonal antibodies of murine origin, which are chimeric and humanized, and also to the amino acid and nucleic sequences coding for those antibodies. The invention also includes use of those antibodies as medicaments for the prophylactic and/or therapeutic treatment of cancers and in diagnostic methods or kits for diseases associated with overexpression of the CD151 protein. Finally, the invention includes products and/or compositions comprising such antibodies in association with antibodies and/or anti-cancer agents or conjugated with toxins and/or radioelements and their use in the prevention and/or treatment of certain cancers.

Abstract: The present invention relates to a method for the preparation of a pharmaceutical composition for the prevention or/and treatment of an influenza virus infection.

Abstract: The present invention relates to new antibodies capable of binding specifically to the human CD151 protein, especially monoclonal antibodies of murine origin, which are chimeric and humanised, and also to the amino acid and nucleic sequences coding for those anitbodies. The invention also includes use of those antibodies as medicaments for the prophylactic and/or therapeutic treatment of cancers and in diagnostic methods or kits for diseases associated with overexpression of the CD151 protein. Finally, the invention includes products and/or compositions comprising such antibodies in association with antibodies and/or anti-cancer agents or conjugated with toxins and/or radioelements and their use in the prevention and/or treatment of certain cancers.

Abstract: In alternative embodiments, the invention provides nucleic acid sequences that are genetic polymorphic variations of the human TMEM216 gene, and TMEM216 polypeptide encoded by these variant alleles. In alternative embodiments, the invention provides methods of determining or predicting a predisposition to, or the presence of, a ciliopathy (or any genetic disorder of a cellular cilia or cilia anchoring structure, basal body or ciliary function) in an individual, such as a Joubert Syndrome (JS), a Joubert Syndrome Related Disorder (JSRD) or a Meckel Syndrome (MKS). In alternative embodiments, the invention provides compositions and methods for the identification of genetic polymorphic variations in the human TMEM216 gene, and methods of using the identified genetic polymorphisms and the proteins they encode, e.g., to screen for compounds that can modulate the human TMEM216 gene product, and possibly treat JS, JSRD or MKS.

Abstract: The present disclosure provides a vector comprising a promoter and a luciferase gene having a nucleic acid sequence as disclosed in SEQ ID NO: 1; a fertilized egg transformed with the present vector; and a transgenic non-human animal overexpressing a luciferase gene from the vector and a method for preparing it. The vector and the animal of the present disclosure have a high expression rate for the luciferase gene, which confers high sensitivity for detection and thus useful for imaging analysis in a variety of research areas.

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: The present invention relates to a fusion protein which comprises at least a functional meganuclease and a viral protein and in particular to fusion protein comprising at least a meganuclease, which recognises and cleaves a specific DNA target sequence and a viral peptide selected from the group Vpr and Vpx or a fragment or derivative thereof; wherein said fusion protein is able to associate with Lentivirus vector particles and following transduction into a host cell recognise and cleave said specific DNA target in vivo. The present Patent Application also relates to a viral particle comprising such a fusion protein and to the use of such fusion proteins and viral particles for gene targeting.

Abstract: Monoclonal antibodies against gonadotropin releasing hormone (GnRH) receptor induce cellular apoptosis of various cancer cells expressing this surface receptor. The monoclonal antibodies and their humanized forms, or fragments thereof, can serve as anti-cancer agents for the treatment of cancer in humans, and can function as analogs of GnRH to affect regulation of reproductive functions or fertility in humans.

Abstract: Meganuclease variants which cleave at least one target in the provirus of a retrovirus and in particular which cleave the genomic insertion of the provirus. The present invention in particular relates to meganuclease variants which cleave the provirus of the Human Immunodeficiency Virus genome following genomic insertion. Vector encoding such variants, as well as to a cell or multi-cellular organism modified by such a vector and use of said meganuclease variants and derived products for genome engineering and for in vivo and ex vivo (gene cell therapy) genome therapy.

Abstract: The present invention relates generally to transgene constructs, transgenic non-human animals comprising transgene constructs, methods of making and methods of using the transgenic non-human animals comprising transgene constructs. An embodiment of the invention relates to methods of assaying the activation of GPCR ligands non-invasively in whole animals, tissue slices, or in native cells using a transgenic model containing a bioluminescent transgene reporter system that is responsive to pathway modulation following ligand binding of GPCR receptors.

Abstract: The invention relates to vectors for the inducible expression of RNA molecules in eukaryotic, particularly mam

Abstract: The present invention relates in a first aspect to a cell model containing chondrocytes whereby said chondrocytes contain a first heterologous nucleic acid sequence operably linked with a mb1 promoter sequence. In another aspect, the present invention relates to a cell model, in particular, to a transgenic animal model whose genome comprises a first heterologous nucleic acid sequence encoding a recombinase and/or restriction enzyme operably linked to a chondrocyte specific promoter, and a second heterologous nucleic acid sequence encoding a target peptide of interest wherein the second nucleic acid sequence further comprises recombination sequences or restriction site for the enzyme encoded by the first heterologous nucleic acid sequence. In addition, methods for screening foreign agent or methods for testing the efficacy and/or efficiency of an agent are provided.

Abstract: The invention relates to antibodies to the tumor-associated antigen CD33 and to the use thereof for immunotargeting CD33-positive cells. The antibodies according to the invention are suitable for use in the field of medicine, pharmaceuticals, and biomedical research. According to the invention, the aim is achieved by means of novel anti-CD33 antibodies comprising the complementary determining regions (CDRs) defined in the claim. The antibodies according to the invention are characterized by a high affinity for human CD33, of the order of magnitude of 1010 mol/l. The CDR sequences according to the invention are suitable in particular for producing recombinant fragments (such as scFv fragments or bispecific antibodies) and for immunotargeting, due to the high affinity thereof.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: The present invention relates to sequence and structural features of single-stranded (ss)RNA molecules required to mediate target-specific nucleic acid modifications by RNA-interference (RNAi), such as target mRNA degradation and/or DNA methylation.

Abstract: The present invention features stabilized/destabilized variant calpastatin proteins and peptides that modulate the stability/activity of calpain for use in analyzing the pathophysiology of diseases associated with calpain activity, facilitating muscle growth and in improving meat tenderization.

Abstract: The present invention relates to methods and systems for inducible ablation of neural cells, in particular non-proliferating cells, such as oligodendrocytes and Schwann cells. The methods and systems include an animal model that can be specifically induced to display phenotypic traits or characteristics of a demyelination condition. The methods and systems disclosed herein are useful for drug screening, by identifying compounds or agents that promote remyelination or reversal of phenotypic traits or characteristics of demyelination conditions.

Abstract: A human artificial chromosome vector comprising a human antibody heavy chain gene, a human antibody light chain gene, and a human antibody surrogate light chain gene.

Abstract: Disclosed are a composition for inhibiting the expression of GA733-2 or for detecting GA733-2, which comprises TREM-2 gene or protein, a transgenic animal containing same, and a method using the same.

Abstract: The invention teaches antisense agents and RNA interference agents useful for treating diseases and conditions the treatment of which can benefit from reducing the expression of double homeobox 4 and/or double homeobox 4c, more particularly facioscapulohumeral muscular dystrophy. Further elaborated are methods, uses and further products employing such agents.

Abstract: A conditional knock-out non-human animal is disclosed. Wherein some cells of the non-human animal but not all the cells comprise a disrupted MO-1 nucleic acid sequence, wherein the disruption results in an inability of the non-human animal to produce detectable levels of the MO-1 protein, as assayed by Southern blot analysis.

Abstract: Provided are hydrolases, including lipases, saturases, palmitases and/or stearatases, and polynucleotides encoding them, and methods of making and using these polynucleotides and polypeptides. Further provided are polypeptides, e.g., enzymes, having a hydrolase activity, e.g., lipases, saturases, palmitases and/or stearatases and methods for preparing low saturate or low trans fat oils, such as low saturate or low trans fat animal or vegetable oils, e.g., soy or canola oils.