Abstract: Substantially pure recombinant TSH has been prepared from a clone comprising complete nucleotide sequence for the expression of the TSH. Diagnostic and therapeutic applications of the synthetic TSH are described.

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 present invention relates to a method to protect a mammal from a disease involving inflammation by treating that mammal with a TGF&bgr;-regulating agent. The present invention also relates to a method for prescribing treatment for a respiratory disease involving an inflammatory response and a method for monitoring the success of a treatment for a respiratory disease involving an inflammatory response in a mammal. Also included in the present invention is a formulation comprising a TGF&bgr;-regulating agent and a compound capable of enhancing the effectiveness of the TGF&bgr;-regulating agent at protecting a mammal from a disease involving inflammation.

Abstract: EF-7 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing EF-7 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The &agr; and &bgr; subunits of the wild-type heterodimers or their variants or their fragments are covalently linked, optionally through a linker moiety. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity.

Abstract: The present invention relates to the Multiple Tumor Suppressor (MTS) genes in mice, their expression products, and their homology to the human MTS genes. The human MTS genes are involved in human cancers. The invention is further related to the use of the MTS genes in the therapy, diagnosis and prognosis of human cancer. The invention further relates to mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkin's lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

Abstract: Proteins such as human &bgr;-interferon or human erythropoietin are prepared by culturing mammalian cells which harbour a nucleic acid sequence comprising: (i) a coding sequence which encodes the desired protein and which is operably linked to a promoter capable of directing expression of the coding sequence in a mammalian cell in the presence of a heavy metal ion; and (ii) a first selectable marker sequence comprises a metallothionein gene and which is operably linked to a promoter capable of directing expression of the metallothionein gene in a mammalian cell in the presence of a heavy metal ion; and optionally (iii) a second selectable marker sequence which comprises a neo gene and which is operably linked to a promoter capable of directing expression of the neo gene in a mammalian cell.

Abstract: Enhanced yields of the platelet-derived growth factor (PDGF) B-chain are obtained using the Pichia pastoris yeast system. Yields of both wild-type and mutant human proteins are enhanced when the yeast is transformed with a vector containing the yeast mating factor promoter fused to a sequence encoding the mature protein. The secreted wild-type protein is indistinguishable from mature 29-32 kDa protein isolated from human and Chinese hamster ovary (CHO) cells. An RKK→EEE mutant exhibited reduced association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK→EEE mutants of either the A- or B-chain inhibited malignant growth in athymic nude mice. Despite altered receptor binding activities, each mutant retained full mitogenic activity when applied to cultured Swiss 3T3 cells. Circular dichroism spectrophotometric analysis of the RKK→EEE mutant revealed a secondary structure indistinguishable from the wild type.

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.

Abstract: Methods for enhancing the production of interferons in animal cell culture are described. These methods rely on the manipulation of the cellular levels of certain inducers of interferon production, in particular cellular levels of double-stranded-RNA-dependent kinase (dsRNA-PKR, or PKR). In cell cultures that overproduce PKR, interferon synthesis is induced to high levels, and significant amounts of interferon can be recovered without conventional induction of interferon by virus.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for zsig45, a novel human protein expressed in thyroid. The polypeptides, and polynucleotides encoding them, may be used for detecting human disease states and chromosomal abnormalities, and as a therapeutic. The present invention also includes antibodies to the zsig45 polypeptides.

Abstract: Single-chain agonists and/or antagonists of the glycoprotein hormones are disclosed. These proteins are of the formula.beta..sup.1 -(linker.sup.1).sub.m -.alpha.-(linker.sup.2).sub.n -.beta..sup.2 (1);or.beta..sup.1 -(linker.sup.1).sub.m -.beta..sup.2 -(linker.sup.2).sub.n -.alpha. (2);or.alpha.-(linker.sup.1).sub.m -.beta..sup.1 -(linker.sup.2).sub.n - .beta..sup.2 (3)wherein each of .beta..sup.1 and .beta..sup.2 has the amino acid sequence of the .beta. subunit of a vertabrate glycoprotein hormone or a variant thereof; ".alpha." designates the .alpha. subunit of a vertabrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that spaces the .beta..sup.1 and .beta..sup.2 subunits at distances from the .alpha. subunit and from each other effective to retain said activity, and each of m and n is independently 0 or 1.

Abstract: The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) that encodes erythropoietin or an insulinotropin (e.g., derivatives of glucagon-like peptide 1 (GLP-1)), methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains that express erythropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells.

Abstract: The invention provides fibroblast growth factor homologous factor (FHF) polypeptides and nucleic acid molecules that encode them. Also included in the invention are diagnostic and therapeutic methods using FHF polypeptides and nucleic acids.

Abstract: A new chemotactic cytokine, NC28 or Monocyte Chemotactic Protein-3 (MCP-3), is provided. Fragments of the cytokine comprising its 13 C-terminal amino acids also exhibit chemotactic activity. The polypeptides may be used as anticancer agents or immunomodulators. DNA encoding the NC28/MCP-3 polypeptides, as well as corresponding vectors and recombinant expression systems, are also provided.

Abstract: Mpl ligand analogs having one or more changed glycosylation sites as compared to a naturally occurring mpl ligand sequence of a corresponding number of amino acids are disclosed. The invention also relates to DNA sequences encoding mpl ligand analogs, recombinant plasmids and host cells for analog expression, and therapeutic compositions including such analogs.

Abstract: A method is described for inducing in vivo proliferation of precursor cells located in mammalian neural tissue by administering to the mammal a fibroblast growth factor and at least one additional growth factor selected from the group consisting of epidermal growth factor, transforming growth factor alpha, and amphiregulin. The method can be used to replace damaged or missing neurons and/or glia. Another method is described for transplanting multipotent neural stem cell progeny into a mammal. The method comprises the steps of administering growth factors to a mammal to induce in vivo proliferation of neural precursor cells, removing the precursor cell progeny from the mammal, culturing the removed cells in vitro in the presence of one or more growth factors that induces multipotent neural stem cell proliferation, and implanting the multipotent neural stem cell progeny into the mammal.

Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. In one embodiment of these single-chain forms, the .alpha. and .beta. subunits of the wild-type heterodimers or their variants are covalently linked, optionally through a linker moiety. A drug may further be included within the linker moiety to be targeted to receptors for these hormones. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity. Another embodiment of the single-chain compounds of the invention comprises two .beta. subunits of the glycoprotein hormones, which .beta. subunits are the same or different. These "two-.beta." forms are antagonists of glycoprotein hormone activity.

Abstract: The recombinant production of PDGF-AB in mammalian cells is disclosed by means of a bicistronic vector system in which an IRES sequence is located between the first and second cistrons and in which the B chain coding gene is located in the first cistron. The disclosed expression unit allows the equilmolar expression of the A and B polypeptide chains.

Abstract: The present invention relates to a macrophage stimulating protein wherein a cysteine residue at position 672 from the N-terminus in the amino acid sequence of native form macrophage stimulating protein is deleted or substituted by another amino acid residue, e.g., an alanine residue; a DNA fragment encoding the protein; a recombinant vector including the DNA fragment; a host cell transformed with the recombinant vector; and a method for culturing the transformed host cell and recovering a macrophage stimulating protein variant from the cultured host cell.

Abstract: A method for preparing and isolating a transformation vector containing CSF/cDNA is described. The method comprises:preparing RNA from a cell that produces CSF;preparing polyadenylated messenger RNA from said RNA;preparing single stranded cDNA from said messenger RNA;converting the single stranded cDNA to double stranded cDNA;inserting the double stranded cDNA into transformation vectors and transforming bacteria with said vector to form colonies;picking pools of 200 to 500 colonies each and isolating plasmid DNA from each pool;transfecting the plasmid DNA into suitable host cells for expressing CSF protein;culturing the transfected cells and assaying the supernatant for CSF activity; andselecting CSF positive pools and screening the colonies used to make the pool to identify a colony having CSF activity. Also described are a cDNA coding for a protein having CSF activity (i.e.

Abstract: The invention relates to a method of cultivating mammalian cells expressing recombinant Factor VIII in a serum-free cell culture medium of the type that normally requires the presence of human serum albumin (HSA) and which is substantially free from fatty acids, fattyacid esters and lipids, but wherein HSA is replaced by at least one glucose or sucrose based polysaccharide having an average molecular weight of from about 10,000 to about 450,000. The invention also relates to such a serum-free cell culture medium.

Abstract: A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.

Abstract: A method of preventing tumor cell metastasis by inhibiting the binding of hepatocyte growth factor/scatter factor ("HGF/SF") with met proto-oncogene protein is described. A method of producing HGF/SF and a cell line for the production of HGF/SF are also described. The met proto-oncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signalling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. The method of the present invention disrupts the Met-HGF/SF autocrine signaling that contributes to the tumorigenic process in tumors of mesenchymal origin, such as sarcomas.

Abstract: Biologically active heterodimeric human fertility hormones composed of two different subunits, each subunit being synthesized in the same cell transformed by at least one cell expression vector having heterologous DNA encoding each subunit with each subunit being controlled by a separate promoter. Preferred human fertility hormones include hCG, hLH and hFSH.

Abstract: A method of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1.0.times.10.sup.6 cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations.

Abstract: A process for production of a desired protein comprising the steps of:a culturing animal cells capable of producing the desired protein in a medium containing trichostatin compounds; andrecovering the desired protein from the culture.

Abstract: A gene is provided which is present in the deletion region of a chromosome common in lung cancer, hepatocellular carcinoma and colorectal cancer and encodes a novel protein, a protein encoded by the gene (PRLTS protein), and a method of discriminating tumor cells. With respect to the human chromosome 8, a detailed gene map was prepared, the chromosome of each of lung cancer, hepatocellular carcinoma and colorectal cancer tissues was analyzed, and a gene encoding a novel protein was cloned to thereby determine the structure thereof. A gene analysis was conducted with the use of a DNA probe derived from the above gene, and consequently mutations in the gene were confirmed in the lung cancer, hepatocellular carcinoma and colorectal cancer tissues.

Abstract: .beta.-interferon is produced in Chinese hamster ovary cells (CHO) in high amounts.

Abstract: Mpl ligand analogs having one or more changed glycosylation sites as compared to a naturally occurring mpl ligand sequence of a corresponding number of amino acids are disclosed. The invention also relates to DNA sequences encoding mpl ligand analogs, recombinant plasmids and host cells for analog expression, and therapeutic compositions including such analogs.

Abstract: The present invention relates to a method of skin regeneration of a wound or burn in an animal or human. This method comprises the steps of initially covering the wound with a collagen glycosaminoglycan matrix, allowing infiltration of the grafted GC matrix by mesenchymal cells and blood vessels from healthy underlying tissue and applying a cultured epithelial autograft sheet grown from epidermal cells taken from the animal or human at a wound free site on the animal's or human's body surface. The resulting graft has excellent take rates and has the appearance, growth, maturation and differentiation of normal skin.

Abstract: A synthetic plasmid in which DNA encoding protein of a feline interferon is integrated, a transformant obtainable by the transformation of a host cell by the use of the synthetic plasmid and a feline interferon having a biological activity given by a protein carrying a specific amino acid sequence, a feline interferon gene encoding the feline interferon, a feline interferon precursor comprised of a cleavable peptide or a signal peptide being linked to the N terminal of the feline interferon, a feline interferon precursor gene encoding the feline interferon precursor and a method for producing the feline interferon, which are applied to the mass production of a feline interferon to be used as a remedy for feline viral disease and tumor.

Abstract: Disclosed herein are improved methods and compositions for achieving enhanced protein production expressed from non-native gene constructs, including single chain sFv and derivative sequences. The methods and compositions are particularly useful for creating stably transfected, contitutively expressing immortalized mammalian cell lines that exhibit high recombinant protein productivity while maintaining a low copy number per cell of the non-native recombinant DNA sequence encoding the protein of interest.

Abstract: The present invention provides methods for preventing occurrence or progression of liver damage using hepatocyte growth factor. In the methods, a preventatively effective amount of the hepatocyte growth factor is administered to the patient. The hepatocyte growth factor can be administered, for instance, prior to administering a hepatotoxic therapy to the patient. The hepatocyte growth factor can further be administered with activin or transforming growth factor-beta to prevent liver damage. Compositions comprising hepatocyte growth factor and activin antagonist or transforming growth factor-beta antagonist are also provided by the invention.

Abstract: Neurogenic differentiation genes and proteins are identified, isolated, and sequenced. Expression of neuroD has been demonstrated in neural, pancreatic, and gastrointestinal cells. Ectopic expression of neuroD in non-neuronal cells of Xenopus embryos induced formation of neurons.

Abstract: Disclosed are CHO cells which are capable of continued production of human LH-RH receptor proteins, or cell membrane fractions thereof; recombinant human LH-RH receptor proteins or partial peptides thereof; methods for screening compounds which have affinity for an LH-RH receptor by contacting the compound with the CHO cells or the cell membrane fractions thereof, or the recombinant human LH-RH receptor proteins or the partial peptides thereof; kits for screening them; the compounds which have affinity for the LH-RH receptor obtained by methods for the screening or kits for the screening; and pharmaceutical compositions containing the compound, thereby being able to early provide prophylactic or therapeutic compositions, for example, for prostate cancer, uterine cancer, breast cancer, a pituitary tumor, endometriosis, hysteromyoma or precocious puberty. They are also useful as a pregnancy controlling composition such as contraceptive or a menstrual cycle controlling composition.

Abstract: Cultured mammalian cells transfected with new vectors comprising full-length or partial .alpha. and .beta. subunit genomic DNA sequences produce significantly higher levels of dimeric glycoprotein hormone than do cells transfected with .alpha. and .beta. subunit cDNA sequences. In cases where only the cDNA clones are available, the cDNA sequences can be used in new expression vectors comprising introns or other important genomic regions from a homologous or heterologous source.

Abstract: New polypeptides having granulocyte colony stimulating activity, preparation thereof and pharmaceutical compositions containing said polypeptides.

Abstract: DNA encoding the prepro inhibin .alpha. and .beta. chains has been isolated. This DNA is ligated into expression vectors and used to transform host cells for the preparation of inhibin or activin. Also provided are prohormone domains and other inhibin .alpha. or .beta. chain derivatives having therapeutic or diagnostic interest. The compositions provided herein are useful in the manipulation of fertility in animals.

Abstract: Purified bone morphogenetic protein-9 (BMP-9) proteins and processes for producing them are disclosed, The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Abstract: The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described. Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.

Abstract: Cultured mammalian cells transfected with new vectors comprising full-length or partial .alpha. and .beta. subunit genomic DNA sequences produce significantly higher levels of dimeric glycoprotein hormone than do cells transfected with .alpha. and .beta. subunit cDNA sequences. In cases where only the cDNA clones are available, the cDNA sequences can be used in new expression vectors comprising introns or other important genomic regions from a homologous or heterologous source.

Abstract: The subject of the present invention is a protein having cytokine type activity, or a precursor of this protein, which comprises the following amino acid sequence (a1): ##STR1## in which Xaa represents Asp or Gly.

Abstract: Disclosed are (1) nucleic acid and amino acid sequences for a novel morphogenic protein; (2) methods for producing and expressing the protein in a biologically active form; and (3) methods for utilizing the protein to induce tissue morphogenesis in a mammal, including methods for increasing a progenitor cell population in a mammal, methods for stimulating progenitor cells to differentiate and maintain their differentiated phenotype in vivo or in vitro, methods for inducing tissue-specific growth in vivo and methods for the replacement of diseased or damaged tissue in vivo.

Abstract: An effective method for the production of a gene product employs recombinant DNA vectors comprising a gene encoding a TIF of a eukaryotic translation factor preceeded by a weak eukaryotic promoter, and at least one internal ribosomal entry site region followed by a gene encoding a desired gene product.

Abstract: A hybrid vector carrying a first and second DNA segments operationally linked thereto, the first DNA segment encoding a protein capable of cross-linking to the cap structure of mRNA and mediating ribosome-binding, and the second DNA segment encoding a polypeptide or protein, the vector being capable of replication, transcription and translation to express the factor and the polypeptide or protein upon transformation of a eukaryotic host, and the polypeptide or protein being expressed at a level higher than the level of expression thereof in the absence of the first DNA segment. A eukaryotic host is transformed with this hybrid vector. Also disclosed is a method of increasing the synthesis of a polypeptide or protein in a eukaryotic host cell.

Abstract: A transformant, which harbors a recombinant vector containing a DNA which codes for human nerve growth factor 2 and a DNA which codes for the pro-region of a nerve growth factor at 5'-terminal of said DNA, produces human nerve factor 2 in stable and large amount in a culture medium.

Abstract: Purified Bone Morphogenetic Protein-11 proteins and processes for producing them are disclosed. Recombinant DNA molecules encoding the BMP-11 proteins are also disclosed. The proteins may be useful in regulating follicle stimulating hormone, such as for contraception, and for the induction of bone, cartilage and/or other connective tissue.

Abstract: Purified Bone Morphogenetic Protein-10 proteins and processes for producing them are disclosed. Recombinant DNA molecules encoding the BMP-10 proteins are also disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Abstract: Purified BMP-15-related proteins and processes for producing them are disclosed. DNA molecules encoding the BMP-15-related proteins are also disclosed. The proteins may be used in the treatment of bone and cartilage and/or other connective tissue defects and in wound healing and related tissue repair.