Abstract: The present invention provides a cell for use in a one-step cell-based assay for an extracellular ligand (e.g., I FN?) that initiates a ligand-specific signal at the nucleus of the cell and for neutralizing antibodies against the extracellular ligand. The cell-based one-step assay allows both the extracellular ligand concentration and the neutralizing antibody titer to be quantified in a single sample (e.g., serum) without the need for sample dilution and addition of exogenous extracellular ligand.

Abstract: The present invention relates to a method for improving post-thaw survival of cryopreserved biological material comprising applying hydrostatic pressure to said biological material; keeping the said biological material at the hydrostatic pressure for a predetermined time period; releasing the hydrostatic pressure; and freezing the said biological material using any protocol applicable thereto.

Abstract: A avian cell line that supports replication of animal or human viruses, which cell line is adapted to animal-product free growth. The cell line is useful for propagating a virus suitable as a live or a killed vaccine and for virus isolation and diagnostic assays.

Abstract: The present invention is directed generally to metal binding compounds which may be added to cell culture media to replace factors required for cultivation of the cells (e.g. transferrin) which are of animal or human origin. More specifically, the invention is directed to metal binding compounds or complexes thereof comprising one or more transition element cations (such as ferrous or ferric ions), which are added to cell and tissue culture medium compositions. The metal binding compounds may be added to the media alone or may be first complexed with a transition metal ion. The invention is also directed to methods of use of such compositions, including, for example, methods for the cultivation of eukaryotic cells, particularly animal cells, in vitro. The invention also relates to compositions comprising such culture media and one or more cells, and to kits comprising one or more of the above-described compositions.

Abstract: A sustained culture of isolated avian gonocytes is provided, as well as a method of making and using the same. A chimeric avian containing an isolated gonocyte and a transgenic avian produced using the chimeric avian are also provided. The cell and method may be employed to make, among other things, transgenic avian that produce a heterologous protein, e.g., a therapeutic protein.

Abstract: The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Abstract: The present invention describes IL-1? binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1?. Binding proteins of the invention have high affinity for IL-1? and neutralize IL-1? activity. A binding protein of the invention can be a full-length antibody or an IL-1?-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1? binding proteins of the invention are useful for detecting IL-1? and for inhibiting IL-1? activity, including in a human subject suffering from a disease or disorder in which IL-1? activity is detrimental.

Abstract: The present invention relates to a nucleic acid molecule as set forth in SEQ ID NO:1 comprising a polynucleotide sequence encoding full length chicken type II collagen (CCII), or a fragment thereof in possession of the same biological functions as well as CCII encoded thereof. It also relates to a method for producing CCII, and its use in the manufacture of a medicament for treating and/or preventing rheumatoid arthritis (RA). The invention specifically relates to a pharmaceutical composition for treating and/or preventing osteoarthritis and RA, to a food or beverage composition, and to a food additive composition, containing CCII prepared according to the method described in this invention, and the use of the nucleic acid molecules of the present application in gene therapy.

Abstract: Methods and compositions are presented for the administration of transposon-based vectors to an animal or human to provide gene therapy to the animal or human

Abstract: The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and/or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

Abstract: The present invention relates to oligopeptide-free cell culture media comprising at least 0.5 mg/L of a polyamine and to methods for cultivating cells in said oligopeptide-free cell culture media comprising at least 0.5 mg/L of a polyamine. The invention also relates to methods for expressing at least one protein in a medium comprising at least 0.5 mg/L of a polyamine and to methods for producing at least one virus in a medium comprising at least 0.5 mg/L of a polyamine.

Abstract: Embodiments of the invention relate to vector constructs and methods for expression of polypeptides including multimeric products such as therapeutic antibodies. Particular constructs allow for the generation of expression products from a single open reading frame (sORF). An embodiment provides an isolated or purified expression vector for generating one or more recombinant protein products comprising a single open reading frame insert; said insert comprising a signal peptide nucleic acid sequence encoding a signal peptide; a first nucleic acid sequence encoding a first polypeptide; a first intervening nucleic acid sequence encoding a first protein cleavage site, wherein said first protein cleavage site is provided by an intein segment of a Ion protease gene of Pyrococcus or a klbA gene of Pyrococcus or Methanococcus, or a modified intein segment derived therefrom; and a second nucleic acid sequence encoding a second polypeptide.

Abstract: The present invention relates to a method for producing a modified foreign chromosome(s) or a fragment(s) thereof, which comprises the steps of: (a) preparing a microcell comprising a foreign chromosome(s) or a fragment(s) thereof, and transferring said foreign chromosome(s) or a fragment(s) into a cell with high homologous recombination efficiency through its fusion with said microcell; (b) in said cell with high homologous recombination efficiency, inserting a targeting vector by homologous recombination into a desired site of said foreign chromosome(s) or a fragment(s) thereof, and/or a desired site of a chromosome(s) derived from said cell with high homologous recombination efficiency, thereby marking said desired site; and (c) in said cell with high homologous recombination efficiency, causing deletion and/or translocation to occur at the marked site of said foreign chromosome(s) or a fragment(s) thereof.

Abstract: The present invention relates to a method for the cultivation of primary cells. The primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The method for the cultivation of primary cells may be one step in a method for the amplification of viruses, such as poxviruses. According to this latter method the primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The cells are then infected with the virus and the infected cells are cultivated in serum free medium until progeny virus is produced.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost innoculation regimen. The present invention relates to a method of virus amplification in primary cells which are cultivated in a serum free medium. Viruses produced by this method are advantageously free of any infectious agents comprised in animal sera.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost inoculation regimen. The present invention relates to a method of virus amplification in primary cells which are cultivated in a serum free medium. Viruses produced by this method are advantageously free of any infectious agents comprised in animal sera.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost inoculation regimen. The present invention relates to a method of virus amplification in primary cells which are cultivated in a serum free medium. Viruses produced by this method are advantageously free of any infectious agents comprised in animal sera.

Abstract: The present invention describes IL-1? binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1?. Binding proteins of the invention have high affinity for IL-1? and neutralize IL-1? activity. A binding protein of the invention can be a full-length antibody or an IL-1?-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1? binding proteins of the invention are useful for detecting IL-1? and for inhibiting IL-1? activity, including in a human subject suffering from a disease or disorder in which IL-1? activity is detrimental.

Abstract: Improved DLL4 binding proteins are described, including antibodies, CDR-grafted antibodies, human antibodies, and DLL4 binding fragments thereof, proteins that bind DLL4 with high affinity, and DLL4 binding proteins that neutralize DLL4 activity. The DLL4 binding proteins are useful for treating or preventing cancers and tumors and especially for treating or preventing tumor angiogenesis, and/or other angiogenesis-dependent diseases such as ocular neovascularization, or angiogenesis-independent diseases characterized by aberrant DLL4 expression or activity such as autoimmune disorders including multiple sclerosis.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: The present invention provides methods for the culture of animal pluripotent stem cells and their differentiated progeny cells, tissues, and organs, and nonhuman animal embryos and fetuses.

Abstract: The invention relates to a method of preventing, inhibiting, arresting or reversing tumourigenesis in a cell as well as a method of inducing apoptosis in a tumour cell. The method includes increasing the amount and/or the activity of a DACT protein, or a functional fragment thereof, in the cell. Also provided is a pharmaceutical composition that comprises a compound of general formula (I), wherein A is CH or N, R1, R4 and R5 are independent from each other H, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group comprising 0-3 heteroatoms. The heteroatoms may be N, O, S, or Si. R4 and R5 may optionally be linked so as to define an aliphatic hydrocarbyl bridge. R2 is H or a halogen such as F, Cl, Br or L. R3 is H, F, Cl or an aliphatic or arylaliphatic group that includes 1-8 main chain carbon atoms and 0-3 heteroatoms. The pharmaceutical composition also comprises a histone deacetylase inhibitor.

Abstract: The present invention provides serum-free cell culture media formulations which are capable of supporting the in vitro cultivation of animal cells. The media comprise at least one nutrient of non-animal derivation, such as at least one plant peptide and/or at least one non-animal or plant lipid and/or fatty acid. The media may further optionally comprise an enzymatic digest or extract of yeast cells. The present invention also provides methods of cultivating animal cells in vitro using these cell culture media formulations. In addition, the media of the present invention can be used for growth of animal cells for virus production.

Abstract: Disclosed are useful constructs and methods for the expression of proteins using primary translation products that are processed within a recombinant host cell. Constructs comprising a single open reading frame (sORF) are described for protein expression including expression of multiple polypeptides. A primary translation product (a pro-protein or a polyprotein) contains polypeptides such as inteins or hedgehog family auto-processing domains, or variants thereof, inserted in frame between multiple protein subunits of interest. The primary product can also contain cleavage sequences such as other proteolytic cleavage or protease recognition sites, or signal peptides which contain recognition sequences for signal peptidases, separating at least two of the multiple protein subunits. The sequences of the inserted auto-processing polypeptides or cleavage sites can be manipulated to enhance the efficiency of expression of the separate multiple protein subunits.

Abstract: The invention provides a genetic reference standard with at least one human genetic reference sequence (having a human DNA sequence containing at least one genetic variant whose presence in the DNA of a human subject is indicative of a pathological condition, a predisposition to a pathological condition, or a predisposition to an adverse reaction to external stimuli, or is indicative of a patient's likely response to a therapeutic intervention, i.e. a variant used in pharmacogenomic analysis) cloned into a non-mammalian animal cell line. There are also provided such reference standards where the human DNA is targeted to specific location in the host genome, using homologous recombination. The invention further provides a method of detecting a genetic variant using such reference standards.

Abstract: Provided is a single construct combining a sequence encoding an RNAi molecule, a sequence encoding a reporter, and a target sequence specific for the RNAi molecule. The construct can be used to determine the potency of the encoded RNAi molecule in a direct and unbiased way. These results can be used to inform the design of potent RNAi molecules of various types and can be extended to several other applications, including: (1) generation of tiled libraries comprising every possible RNAi molecule-encoding sequence for a given gene target; (2) large-scale parallel validation of RNAi molecules targeting many genes to generate validated RNAi molecule-encoding libraries; (3) experimental comparison of design algorithms and strategies; and (4) investigation of RNAi biology in target site mutagenesis assays by screening pools containing single nucleotide changes in target sites and/or in the RNAi molecule to identify the most relevant sequence characteristics of potent RNAi-target site predictions.

Abstract: The present invention is related to a method for inducing in vitro the differentiation of stem cells or somatic cells towards germinal cells, comprising the following steps: cultivating said stem cells or somatic cells in a medium allowing their differentiation, and collecting the germinal cells from the culture medium, wherein said cells are cells transformed with an exogenous genetic construction comprising at least a Vasa gene. Germinal cells such as obtained and chimeric animals are also an object of this invention.

Abstract: This invention relates to immortalized avian cells, including those deposited under accession numbers 09070701, 09070702, and 09070703 at the ECACC, and to the use of these cells for the production of viruses. The cells according to the invention are particularly useful for the production of recombinant viral vectors which can be used for the preparation of therapeutic and/or prophylactic compositions for the treatment of animals and more particularly humans.

Abstract: The invention provides for a method for aggregating dermal papilla cells or dermal sheath cells or a combination thereof, the method comprising: growing dermal papilla cells or dermal sheath cells or a combination thereof in suspension culture; and contacting the culture with an effective amount of an enzyme, wherein a substrate of the enzyme is an extracellular matrix molecule in the suspension culture, so as to aggregate dermal papilla cells or dermal sheath cells. The culture may be a hanging drop culture and the enzyme may be a hyaluronidase.

Abstract: The invention relates to methods of increasing the titre of a protein of interest in a cell as well as the improved production and purification of optimised biomolecules, one component of which is the domain CH3. A frequently observed effect in biomolecules is the cleaving of the C-terminal amino acid(s), e.g. the C-terminal lysine. The usually incomplete processing of the heavy chain of antibodies for example leads to product heterogeneity. To prevent this product heterogeneity the corresponding codon of the C-terminal lysine of the heavy antibody chain has been deleted by recombinant DNA technology. These optimised antibodies lead to a product titre which is higher than in the wild-type. In addition, they prove advantageous during purification by having better elution characteristics as a result of the reduced charge heterogeneity.

Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.

Abstract: The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and/or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

Abstract: The present invention relates to recombinant vaccinia viruses derived from the modified vaccinia virus Ankara (MVA) and containing and capable of expressing foreign genes which are inserted at the site of a naturally occurring deletion in the MVA genome, and the use of such recombinant MVA viruses for the production of polypeptides, e.g. antigens or therapeutic agents, or viral vectors for gene therapy, and the use of such recombinant MVA viruses encoding antigens as vaccines.

Abstract: Fusion proteins and DNA conjugates are disclosed which contain a TLR/CD40/agonist and optional antigen combination. The use of these protein and DNA conjugates as immune adjuvants and as vaccines for treatment of various chronic diseases such as HIV infection is also provided.

Abstract: The instant invention provides soluble fusion protein complexes and IL-15 variants that have therapeutic and diagnostic use, and methods for making the such proteins. The instant invention additionally provides methods of stimulating or suppressing immune responses in a mammal using the fusion protein complexes and IL-15 variants of the invention.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: The present invention relates to novel sequences of H. contortus and the proteins encoded therein. This invention also relates to immunogenic compositions, methods for their preparation and the diagnostic, prophylactic or therapeutic use of these sequences and the proteins encoded therein.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating an inflammatory disease or disorder. The bacterium includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: Method of culturing embryonic stem (ES) cells of avian origin includes the steps of: a) suspending ES cells originating from the blastoderm disk of fertilized un-incubated avian egg(s) in a basal culture medium supplemented with: insulin-like growth factor-1 (IGF-1) and ciliary neurotrophic factor (CNTF); and animal serum; and, optionally, at least one growth factor selected from among interleukin 6 (II-6), interleukin 6 receptor (II-6R), stem cell factor (SCF), fibroblast growth factor (FGF), leukemia inhibitory factor (LIF), interleukin 11 (II-11), oncostatin and/or cardiotrophin; b) seeding the suspension of ES cells obtained in step a) on a layer of feeder cells and further culturing the ES cells for at least 2 to 10 passages; c) optionally, removing at least one growth factor selected from among SCF, FGF, II-6, II-6R, LIF, oncostatin, cardiotrophin and II-11 from the culture medium; and d) further culturing the ES cells in the medium of step c) on a layer of feeder cells.

Abstract: The invention generally relates to the field of recombinant protein production. More particularly, the invention relates to the use of avian embryonic derived stem cell lines, named EBx®, for the production of proteins and more specifically glycoproteins such as antibodies. The invention is useful for the production of monoclonal IgG1 antibody subtype having high cell-mediated cytotoxic activity. The invention relates to the use of such antibodies as a drug to treat cancers and inflammatory diseases.

Abstract: The present invention encompasses IL-1? binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1? and neutralize IL-1? activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1? and for inhibiting IL-1? activity, e.g., in a human subject suffering from a disorder in which IL-1? activity is detrimental.

Abstract: The present invention relates to a method for producing avian cell lines, comprising gradual or complete withdrawal of growth factors, serum and/or feeder layer so that the established lines are adherent or nonadherent cells capable of proliferating indefinitely in a basic culture medium. The invention also relates to the cells derived from such lines which are particularly useful for the production of substances of interest.

Abstract: The present invention provides methods for the detection of biliverdin in birds (avian species) and reptiles.

Abstract: This invention relates to a method for stably expressing a transgene integrated into the genome of an animal cell or of an animal over a long period. Specifically, this invention provides: an approximately 2.5 kb XhoI-BamHI fragment (or XB fragment) derived from the Evx2-Hoxd13 intergenic region of the animal genome, or a homologue thereof; a DNA containing a foreign DNA wherein the DNA has been inserted between the two essentially identical XB fragments or homologues thereof; a vector, animal cell, or nonhuman mammalian animal containing said DNA; and use of the vector, animal cell, or nonhuman mammalian animal for production of a substance or therapy.

Abstract: A chicken embryonic stem cell is established, which stably has pluripotency and an ability of being differentiated into a germ cell. For evaluating on whether or not the chicken embryonic stem cell can be applied to genetic modification technique, detection is made on a protein which serves as an indicator of the ability of being differentiated into a germ cell. This provides (i) a chicken embryonic stem cell applicable to genetic modification technique and (ii) a method for evaluation of the chicken embryonic stem cell.

Abstract: The present invention relates to a method for replicating poxviruses such as vaccinia virus comprising the steps of inoculating avian embryonic stem cells with viral particles and culturing said cells in a basal medium until cells lysis occurs and newly produced viral particles are released in said medium.

Abstract: Methods and compositions are presented for the administration of transposon based vectors to an animal or human to provide gene therapy to the animal or human.

Abstract: Disclosed are recombinant host cells suitable for degrading an oligosaccharide that have been optimized for growth and production of high yields of ethanol, and methods of making and using these cells. The invention further provides minimal media comprising urea-like compounds for economical production of ethanol by recombinant microorganisms. Recombinant host cells in accordance with the invention are modified by gene mutation to eliminate genes responsible for the production of unwanted products other than ethanol, thereby increasing the yield of ethanol produced from the oligosaccharides, relative to unmutated parent strains. The new and improved strains of recombinant bacteria are capable of superior ethanol productivity and yield when grown under conditions suitable for fermentation in minimal growth media containing inexpensive reagents. Systems optimized for ethanol production combine a selected optimized minimal medium with a recombinant host cell optimized for use in the selected medium.

Abstract: The present invention encompasses IL-12p40 binding proteins, particularly antibodies that bind human interleukin-12 (hIL-12) and/or human IL-23 (hIL-23). Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-12 and/or hIL-23 and neutralize h IL-12 and/or hIL-23 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and/or hIL-23 and for inhibiting hIL-12 and/or hIL-23 activity, e.g., in a human subject suffering from a disorder in which hIL-12 and/or hIL-23 activity is detrimental.