Abstract: The present invention relates to the qualitative and quantitative validation of marker indices, especially for medical diagnosis and particularly for the determination of the growth fraction in a sample with antibodies against the Ki-67 protein. Diagnostic kit for the quantification of a cell fraction labeled by a marker for in vitro diagnosis, characterized in that a pseudo-tissue is used for the intra- and inter-assay standardization of the marker index.

Abstract: Recombinant immunotoxins containing a cytotoxic RNAse fused to an antibody or antibody fragment may be produced in mammalian cell culture. Surprisingly, immunotoxins containing a cytotoxic RNAse fused to the N-terminus of one antibody variable domain can be prepared and retain the ability to specifically bind antigen. The immunotoxins may be used in a variety of therapeutic methods for treating diseases or syndromes associated with unwanted or inappropriate cell proliferation or activation.

Abstract: The present invention relates to a method for increased production of a secreted, recombinant protein product through the introduction of molecular chaperones in a mammalian host cell. The present invention also relates to a mammalian host cell with enhanced expression of a secreted recombinant protein product by coexpressing at least one chaperone protein.

Abstract: The present invention includes novel recombinant canine herpes virus (CHV) and novel recombinant CHV genomes, and particularly to those CHV and CHV genomes that contain heterologous nucleic acid molecules. The present invention also relates to the use of such genomes and viruses in a variety of applications, including as therapeutic compositions to protect animals from disease. The present invention also relates to novel isolated CHV nucleic acid molecules, to CHV proteins encoded by such nucleic acid molecules, and to antibodies raised against such CHV proteins as well as to the use of such CHV nucleic acid molecules, proteins and antibodies as therapeutic compositions to protect an animal from CHV. The present invention also includes constructs comprising CHV nucleic acid molecules that include heterologous nucleic acid molecules, to recombinant vectors including such constructs, and to the use of such constructs and vectors in the production of recombinant CHV and recombinant CHV genomes.

Abstract: Novel fusion polypeptide ligands that bind Eph family receptors or the Tie-2 receptor are identified, and methods for making the fusion polypeptide ligands in biologically active form are described. Nucleic acids encoding these novel fusion polypeptide ligands enable production of the fusion polypeptide ligands. The method of making the nucleic acids and the fusion polypeptide ligands is broadly applicable to the production of polypeptide ligands in general, resulting in improved affinity and/or increased activity of the ligand when compared to its native form.

Abstract: The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells.

Abstract: The present invention provides tangible means and methods for stimulation of angiogenesis via enhanced endothelial expression of core proteins having a syndecan-4 cytoplasmic region intracellularly. The tangible means include a prepared DNA sequence fragment having separate and individual DNA sequenced portions coding for an heparan sulfate binding extracellular domain, a central transmembrane domain, and a cytoplasmic domain coding for the syndecan-4 polypeptide. The prepared DNA sequence unitary fragment may be delivered to endothelial cells in-situ, both under in-vivo and/or in-vitro conditions, using suitable expression vectors including plasmids and viruses. The resulting transfected endothelial cells overexpress heparan sulfate binding, core proteins; and the resulting overexpression of these proteoglycan entities causes stimulation of angiogenesis in-situ.

Abstract: The gene coding for human erythropoietin (EPO) was obtained from human genomic DNA. Thc gene used does not include sequences from regions at i 5′ of the first translated ATG and ii 3′ of the stop codon of the EPO gene. The gene was cloned into an expression plasmid for eukaryotic cells that have as sole expression control elements the early promoter of the SV40 virus and its polyadenylation signal. Recombinant cells resulting from transfection with genetic constructs used provide an unexpectedly high level of protein expression of 50 mg of recombinant EPO per liter of culture medium per day.

Abstract: Glycosylated or nonglycosylated proteins of the formula FSH&bgr;-(linker1)n1-LH&bgr;(1-X)-(linker2)n2-&agr; wherein FSH&bgr; is a vertebrate follicle stimulating hormone &bgr; subunit or a variant thereof; LH&bgr;(1-X) refer's to a &bgr; subunit of a vertebrate luteinizing hormone containing positions 1-X where X is an integer of 114-121 or a variant thereof; each “linker” is a hydrophilic, flexible amino acid sequence containing 1-100 amino acid residues; each n is a 0 or 1; and &agr; is the &agr; subunit of a vertebrate glycoprotein hormone or a variant thereof are useful in protocols to enhance fertility in humans and in animals.

Abstract: Immunostimulatory compositions that contain fused cells formed by fusion between dendritic cells and non-dendritic cells, methods of using these compositions, and methods of generating dendritic cell hybrids.

Abstract: A novel feline cytokine protein having the activity to enhance the cytotoxic activity of feline cytotoxic T lymphocytes, a DNA sequence coding for said protein, a recombinant DNA for expressing said protein, an expression vector comprising said recombinant DNA, a transformant which is transformed with said expression vector, a process for preparing said protein by culturing said transformant, and an antibody against said protein are provided. The novel feline cytokine protein of the present invention is a heterologous dimer comprising FLAF p35 and FLAF p40 and can be used for treating feline infectious diseases such as feline herpes virus type 1 (FHV-1) or feline calicivirus (FCV).

Abstract: Proteins containing any of the amino acid sequences represented by Sequence No. 1 to Sequence No. 2 or by Sequence No. 4 to Sequence No. 25 and DNAs encoding said proteins exemplified by cDNAs containing any of the base sequences represented by Sequence No. 26 to Sequence No. 50. Said proteins can be provided by expressing cDNAs encoding human proteins having transmembrane domains and recombinants of these human cDNAs.

Abstract: Retroviral vectors which encode interferon alpha are disclosed. These canbe used to produce recombinant transduced cells. Both the vectors and the recombinant transduced cells can be used therapeutically. The cells can also be used to produce alpha interferon.

Abstract: The present invention makes available rapid, effective assays for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assays enable rapid screening of large numbers of polypeptides in a library to identify those polypeptides which induce or antagonize receptor bioactivity. The subject assays are particularly amenable for identifying agonists and antagonists for orphan receptors. In particular the present invention makes available novel ligand agonists of human formyl peptide receptor like-1 (FPRL-1) receptors. These novel ligand agonists are used in the assays of the invention to identify modulators of FPRL-1 receptor.

Abstract: Methods for stimulating a T cell response to a tumor cell in a subject with a tumor which involve modifying the tumor cell to express a CD2 ligand and a CD28 or CTLA4 ligand, are disclosed. Methods wherein the tumor cell is obtained from the subject and modified ex vivo to form a modified tumor cell and then the modified tumor cell is administered to the subject, are also disclosed.

Abstract: This invention generally provides polypeptides comprising a noncleavable form of a Fas ligand and having a capacity to activate a Fas receptor-mediated pathway involved in cell death, pharmaceutical compositions of such polypeptides, nucleic acids encoding such polypeptides, and cell lines capable of expressing these nucleic acids. Also provided are therapeutic and prophylactic methods of using such polypeptides, compositions, and cells lines for treating patients suffering from disorders resulting from dysregulation or inappropriate stimulation of the Fas receptor-mediated pathway.

Abstract: A method for discovering molecules that regulate cell signaling specific to the dual presence of Duffy antigen receptor for chemokines (DARC) and a chemokine receptor selected from the group consisting of a CXC receptor, a CC receptor and a CXXXC receptor, the method comprising providing a cell that co-expresses DARC and the chemokine receptor; incubating the molecules with the cell; measuring the cell signaling in the cell specific to the dual presence of DARC and the chemokine receptor; and determining whether the cell signaling specific to the dual presence of DARC and the chemokine receptor is regulated by the molecules

Abstract: Glycosylated interleukin-2 muteins are described. A method of producing the muteins using mammalian cells is included. The muteins may be incorporated into pharmaceutical preparations useful for, e.g., cancer therapy.

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: The invention relates to nucleotide sequences encoding human interleukin-3 (hIL-3) as well as recombinant DNAs, expression cassettes, transformed host cells, and recombinant expression methods comprising such sequences. Additionally, the invention describes proteins having hIL-3 activity, as purified, recombinantly produced, or fusion protein forms of hIL-3, as well as methods of using such proteins to produce antibodies capable of immunospecific reaction with hIL-3.

Abstract: Embodiments of the present invention are directed to non-naturally occurring cells and methods for screening compositions and genes which interact with interleukin 1 beta and interleukin-1 beta converting enzyme (ICE) processing, methods and non-naturally occurring cells for making ICE, and agonists and inhibitors of ICE.