Abstract: The present invention provides purified and isolated polynucleotide sequences encoding a novel human macrophage-derived C—C chemokine designated MDC. Also provided are materials and methods for the recombinant production of the chemokine, and purified and isolated chemokine protein.

Abstract: The present invention relates to a novel Neutrokine-a, and a splice variant thereof designated Neutrokine-aSV, polynucleotides and polypeptides which are members of the TNF family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-a and/or Neutrokine-aSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-a and/or Neutrokine-aSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Neutrokine-a and/or Neutrokine-aSV activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: The present invention relates to a novel Neutrokine-&agr; protein which is a member of the TNF protein family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-&agr; protein including soluble forms of the extracellular domain. Neutrokine-&agr; polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Neutrokine-&agr; activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.

Abstract: A novel human cytokine, JE factor, and processes for producing it are disclosed. JE may be used in pharmaceutical preparations for stimulating and/or enhancing immune responsiveness and in wound healing and related tissue repair. containing the factor.

Abstract: To solve the problem of drug tolerence and side effects in antiinflammatory agents, immunosuprressive agents and antiviral agents having been put into practical use, it is intended to provide a novel therapy for inflammation and novel antiinflammatory agents with the use of an ETS transcription factor which regulates the gene expression of an inflammartory cytokine GM-CSF and a bactericidal peptide &bgr;-defensin. Namely, expression regulators for the inflammatory cytokine GM-CSF and/or &bgr;-defensin in epithelial cells and antiinflammatory agents which comprise an ETS transcription factor having a gene transcription regulatory activity or a gene encoding the same, or a substance regulating the function of ETS transcription factor or a gene encoding the same, more specifically, a transcription regulatory protein myeloid Elf-1 like factor (MEF) or a gene encoding the same, or a substance regulating the function of the MEF protein or a gene encoding the same.

Abstract: Disclosed is substantially pure eotaxin DNA sequence and eotaxin polypeptide, and methods of using such DNA and polypeptide to direct chemotaxis of eosinophils. Methods are provided for the treatment diseases and disorders such as inflammation and tumorigenesis.

Abstract: The invention concerns a process for the recombinant production of S-layer proteins in gram-negative host cells. Furthermore the nucleotide sequence of a new S-layer gene and processes for the production of modified S-layer proteins are disclosed.

Abstract: A method of treatment of and composition for human degenerative neurologic diseases discloses the administration of therapeutically amounts of an enhancement agent, such as thrombopoietin, to enhance the repair of neurons, including re-myelinization. A regulatory agent, such as thyroid hormone or thyrotropin, may also be included as part of the method and composition as a regulator of cell division and oligodendroglia production.

Abstract: An analogous vaccine to tumor cells is produced by transducing the tumor cells with a herpes simplex virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells. The tumor cells may transduced with the herpes simplex amplicons ex vivo or in vivo. Suitable immunomodulatory proteins include cytokines, for example, interleukins, interferons, and chemokines such as RANTES; intercellular adhesion molecules, for example ICAM-1 and costimulatory factors such as B7.1. The tumor cells may also be transduced with one or more species of amplicon containing genes for two or more different immunomodulatory proteins.

Abstract: There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human myeloid progenitor inhibitory factor-1 (MPIF-1) polypeptide (previously termed MIP-3 and chemokine &bgr;8 (CK&bgr;8 or ckb-8)); a human monocyte-colony inhibitory factor (M-CIF) polypeptide (previously termed MIP1-&ggr; and chemokine &bgr;1 (CK&bgr;1 or ckb-1)), and a macrophage inhibitory protein-4 (MIP-4), as well as MPIF-1, M-CIF and/or MIP-4 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same.

Abstract: The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-&bgr; dependent-programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that the RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG island located around RUNX3 exon (1). The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. CpG island around RUNX3 exon (1) could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and there by induce RUNX3 expression but also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.

Abstract: This invention relates to an isolated nucleic acid fragment encoding scorpion toxins that are Na-channel modifiers. The invention also relates to the construction of a chimeric gene encoding all or a substantial portion of the Na-channel modifier, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the Na-channel modifier in a transformed host cell.

Abstract: A mammalian cytokine-like polypeptide, called Mammalian Cytokine-like polypeptide-10, (Zcyto10), polynucleotides encoding the same, antibodies which specifically bind to the polypeptide, and anti-idiotypic antibodies which bind to the antibodies. Zcyto10 is useful for promoting the healing of wounds and for stimulating the proliferation of platelets.

Abstract: A mammalian cytokine-like polypeptide, called Mammalian Cytokine-like polypeptide-10, (Zcyto 10), polynucleotides encoding the same, antibodies which specifically bind to the polypeptide, and anti-idiotypic antibodies which bind to the antibodies. Zcyto 10 is useful for promoting the healing of wounds and for stimulating the proliferation of platelets.

Abstract: Novel chemokines from mammals, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding said chemokines. Chemokine receptors are also provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Novel B7-like polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length B7-like proteins, the invention further provides isolated B7-like fusion proteins, antigenic peptides, and anti-B7-like antibodies. The invention also provides B7-like nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a B7-like gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Novel stem cell factors, oligonucleotides encoding the same, and methods of production, are disclosed. Pharmaceutical compositions and methods of treating disorders involving blood cells are also disclosed.

Abstract: The present invention relates to a novel I-FLICE-1 or I-FLICE-2 protein which is a novel inhibitor of TNFR-1 and CD-95 induced apoptosis. In particular, isolated nucleic acid molecules are provided encoding the human I-FLICE-1 or I-FLICE-2 protein. I-FLICE-1 or I-FLICE-2 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of I-FLICE-1 or I-FLICE-2 activity. Also provided are therapeutic methods for treating diseases and disorders associated with apoptosis.

Abstract: The present invention relates to a method for improving homogeneity and/or secretion of a recombinant protein of interest expressed in mammalian cells by replacing the endogenous signal peptide sequence of the DNA encoding the protein of interest with that of human hGH. The invention also relates to DNA expression vectors containing the sequence encoding such proteins fused to the signal peptide sequence of the hGH and to cells harboring such vectors.

Abstract: The invention provides novel polynucleotides and polypeptides encoded by such polynucleotides and mutants or variants thereof that correspond to a novel human secreted neurotrimin-like polypeptide. These polynucleotides comprise nucleic acid sequences isolated from cDNA library from human thalamus (Hyseq clone identification number 10468562). Other aspects of the invention include vectors containing processes for producing novel human secreted neurotrimin-like polypeptides, and antibodies specific for such polypeptides.

Abstract: The present invention relates to methods and compositions for modifying peptides, polypeptides and proteins with polymers, especially glyco-mimetic polymers, so as to improve their biological activity or pharmacokinetic properties. The invention further provides methods and uses for such polymer-modified peptides, polypeptides and proteins. The invention is particularly suitable for use in the synthesis of polymer-modified synthetic bioactive proteins (FIG. 1D), and of pharmaceutical compositions that contain such proteins.

Abstract: The present invention relates to a vaccine for increasing the immunogenicity of a tumor antigen thus allowing treatment of cancer, as well as a vaccine that increases the immunogenicity of a viral antigen, thus allowing treatment of viral infection, including immunodeficiency virus (HIV) infection. In particular, the present invention provides a fusion protein comprising a viral chemokine fused to either a tumor antigen or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing viral infection.

Abstract: Mutants of CC chemokines, which contain at least two mutations in the cationic site of the 40's loop and which, relative to the wild-type molecule, have a reduced GAG-binding activity. In particular it has been found that such mutated chemokines are effective in the treatment of multiple sclerosis and/or demyelinating diseases. A triple mutant of RANTES is the compound showing the best results.

Abstract: A process for the production of a protein by cell culture, said process comprising culturing eukaryotic cells which constitutively produce said protein in a medium which comprises an alkanoic acid and/or salt thereof at a maintained concentration of less than 0.1 mM.

Abstract: The present invention provides an isolated DNA molecule that codes for a cell-surface binding protein in human monocytes and macrophages. In addition, an amino acid sequence derived from the nucleotide sequence is provided. The newly-identified cell-surface binding protein described herein is instrumental in the apoB-mediated cellular uptake of plasma chylomicrons and remnants and hypertriglyceridemic triglyceride-rich lipoproteins in an ApoE- and lipoprotein lipase- and heparin sulfate proteoglycan-independent pathway. The new human macrophage receptor has been cloned and uniquely, binds TGRLP via apolipoprotein B48, the marker of dietary TGRLP (apoB48R). This process rapidly converts macrophages and apoB48R-transfected Chinese hamster ovary cells in vitro into lipid-filled “foam cells,” hallmarks of atherosclerotic lesions. The apoB48R cDNA (3744 bp) encodes a novel protein with no known homologs. Its ˜3.8 kb mRNA is expressed primarily by reticuloendothelial cells.

Abstract: Apoptosis-modifying fusion polypeptides, and the corresponding nucleic acid molecules, are disclosed. Pharmaceutical compositions comprising these polypeptides, and the use of these polypeptides to modify apoptosis are also provided.

Abstract: A method for identifying compounds that can be useful for producing analgesia is disclosed. In particular, the method involves providing preparation of a cell, that expresses an alpha1B adrenergic receptor, combining a test compound with the cell preparation, measuring the effect of the test compound on the alpha1B receptor activity, and evaluating the compound thus identified for analgesic activity.

Abstract: The present invention provides nucleotide and amino acid sequences that identify and encode a novel expressed chemokine (ADEC) from inflamed adenoid tissue. The present invention also provides for antisense molecules to the nucleotide sequences which encode ADEC, expression vectors for the production of purified ADEC, antibodies capable of binding specifically to ADEC, hybridization probes or oligonucleotides for the detection of ADEC-encoding nucleotide sequences, genetically engineered host cells for the expression of ADEC, diagnostic tests for inflammation or disease based on ADEC-encoding nucleic acid molecules or antibodies capable of binding specifically to ADEC.

Abstract: The present invention provides a human tumor suppressor protein having the amino acid sequence of SEQ ID NO: 2; a polynucleotide encoding the tumor suppressor protein; an expression vector containing the polynucleotide; a microorganism or animal cell transformed with the expression vector, a method for suppressing proliferation of a cancer cell which comprises introducing the expression vector into a cancer cell to induce apoptosis thereof; and a pharmaceutical composition for preventing or treating cancer which comprises a therapeutically effective amount of the polynucleotide and a pharmaceutically acceptable carrier.

Abstract: The present invention provides polynucleotides encoding NF-kB-associated polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these NF-kB-associated polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: Disclosed are human G-CSF isoforms having a modified amino acid sequence containing a glycosylation sequence Asn-X-Ser/Thr (N-X-S/T) at one or more specific amino acid positions according to the present invention, genes encoding the human G-CSF isoforms, and expression vectors carrying the genes, eukaryotic cells transformed or transfected with the expression vectors. Also, the present invention discloses a method of preparing a glycosylated human G-CSF isoform, comprising the steps of culturing the transformant or transfectant and isolating a glycosylated human G-CSF isoform from the culture supernatant or cell lysates, a human G-CSF isoform prepared by the method, and a pharmaceutical composition comprising the human G-CSF isoform.

Abstract: The activity of an expression product of a gene introduced into a living body can be regulated by the coexistence of a protein (interfering substance) that interferes with the activity of the expression product. Receptors of the expression product and such may be used as the interfering substance. The activity of an overexpressed product of a gene introduced in gene therapy can be regulated. The administration of an interfering substance can be achieved by in vivo expression of the gene encoding the substance.

Abstract: According to the invention, there is provided a vector for the expression of immunoglobulin-cytokin fusion proteins in malignant B cells at least containing operably linked to each other

Abstract: The invention relates to protein complexes and fusion proteins including at least two different cytokine molecules. The protein complexes and fusion proteins may further include a targeting moiety such as a region of an immunoglobulin. Methods of using the protein complexes and fusion proteins are also disclosed.

Abstract: Disclosed are novel polypeptides possessing part or all of the primary structural conformation and one or more of the biological properties of a mammalian (e.g., human) pluripotent granulocyte colony-stimulating factor (“hpG-CSF”) which are characterized in preferred forms by being the product of procaryotic or eucaryotic host expression of an exogenous DNA sequence. Sequences coding for part or all of the sequence of amino acid residues of hpG-CSF or for analogs thereof may be incorporated into autonomously replicating plasmid or viral vectors employed to transform or transfect suitable procaryotic or eucaryotic host cells such as bacteria, yeast or vertebrate cells in culture. Products of expression of the DNA sequences display, e.g., the physical and immunological properties and in vitro biological activities of isolates of hpG-CSF derived from natural sources. Disclosed also are chemically synthesized polypeptides sharing the biochemical and immunological properties of hpG-CSF.

Abstract: The present invention provides method of increasing the biological activity of KC, gro-&agr;, gro-&bgr;, and gro-&ggr; proteins, truncated and modified proteins characterized by having biological activity at least 1 log better than the full-length protein, and pharmaceutical compositions containing same.

Abstract: The present invention provides, as a gene encoding an antigen recognized by a G-CSF inducing antibody, a gene encoding any one of the following proteins: (a) a protein having an amino acid sequence shown in SEQ ID NO; 2; (b) a protein having an amino acid sequence comprising a deletion, substitution, addition or insertion of one or several amino acids with respect to the amino acid sequence shown in SEQ ID NO: 2, and having a binding ability for an antibody which induces and secretes a granulocyte colony-stimulating factor or a fragment thereof: or (c) a protein having at least 50% or more homology with the amino acid sequence shown in SEQ ID NO: 2, and having a binding ability for an antibody capable of inducing and secreting a granulocyte colony-stimulating factor or a fragment thereof.

Abstract: The present invention relates generally to Activity Dependent Neurotrophic Factor III (ADNF III), also known as Activity Dependent Neuroprotective Protein (ADNP). More particularly, the present invention relates to nucleic acid sequences encoding ADNF III polypeptides; ADNF III polypeptides encoded by such nucleic acid sequences; antibodies to ADNF III polypeptides; and methods of using such ADNF III polypeptides for the treatment of neurological deficiencies and for the prevention of cell death associated with (1) gp120, the envelope protein from HIV; (2) N-methyl-D-aspartic acid (excito-toxicity); (3) tetrodotoxin (blockage of electrical activity); and (4) &bgr;-amyloid peptide, a substance related to neuronal degeneration in Alzheimer's disease.

Abstract: This invention relates to proteins, termed Q14507, CAA53971.2 and CAC17141.1 herein identified as cytokines and to the use of these proteins and nucleic acid sequences from the encoding genes in the diagnosis, prevention and treatment of disease.

Abstract: This application relates to antibodies reactive with a novel homogenous human cytokine, Natural Killer Stimulator Factor (NKSF), having the ability to induce the production of gamma interferon in vitro in human peripheral blood lymphocytes, and a pharmaceutical preparation containing such antibodies.

Abstract: This invention relates to the therapeutic induction of supra-normal apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNF&agr; promoter enhancer attached to a functional copy of a minimal TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNF&agr; promoter. Examples of apoptosis-inducing genes include caspase-3, caspase-4, caspase-5, and Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNF&agr;.

Abstract: Human chemokine polypeptides and DNA (RNA) encoding such chemokine polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemokine polypeptides for the treatment of leukemia, tumors, chronic infections, autoimmune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such chemokine polypeptides and their use as a therapeutic to treat rheumatoid arthritis, autoimmune and chronic inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed.

Abstract: The present invention relates to compositions comprising heteromultimeric complexes, and particularly heterotrimeric complexes, of TNF ligand family members, and methods of using such complexes in the detection, prevention, and treatment of disease. Heteromultimeric TNF ligand polypeptide complexes comprising human TNF ligand polypeptides, including soluble forms of the extracellular domains, as well as membrane bound forms of TNF ligand polypeptides are provided. Heteromultimeric TNF ligand polypeptide complexes are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of heteromultimeric TNF ligand polypeptide complexes. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: Subject matter of the invention are antibody-cytokine fusion proteins having proapoptotic and immune modulating properties, but wherein the cytokine moiety a priori has a bioactivity which is very low or restricted to certain receptor subtypes. These reagent exert their full biological activity via the corresponding cytokine receptor(s) only after antibody-mediated binding of the fusion protein to a specific cell membrane-expressed target molecule. By suitable choice of the antibody specificity, the cytokine activity is directed to the tissue, e.g. tumour tissue, to be treated, and a therapeutic agent can be produced being specifically designed/optimised for the respective indication/tumour entity.

Abstract: Transformed cells designed to express a recombinant human SMBP at an elevated level to the extent that its ligand-binding activity can be measured, and cellular membrane fractions thereof; recombinant human SMBPs isolated from the transformed cells or the cellular membrane fractions thereof; a screening system for human SMBP agonists/antagonists characterized by utilizing the transformed cells, the cellular membrane fractions thereof or the isolated recombinant human SMBPs; and human SMBP agonists or antagonists obtainable by the screening system, are provided by deleting the polythymidine sequence from the base sequence of the 3′-untranslated region.

Abstract: The present invention relates to a variant of Lkn-1(shLkn-1) with enhanced biological activity, which is a truncated form of Lkn-1, a process for preparing a recombinant shLkn-1 by employing expression vector therefor and pharmaceutical application of the said protein. shLkn-1 is generated by missing 26 amino acid residues from the amino terminus of Lkn-1 to contain 66 amino acids. Recombinant shLkn-1 inhibits colony formation and cell proliferation in vivo, which suggests that it can be used as a potential drug for the antibody production, the treatment during HIV-1 infection, the protection of bone marrow stem cells during chemotherapy or radiotherapy, and the inhibition of leukemia.

Abstract: The present invention relates to the IL-12p40 subunit mutant gene which can produce IL-12 (interleukin 12) of human and mouse origin with high activity, the expression vector including above mutant gene and the use of them to DNA vaccine adjuvant. Particularly, it relates to IL-12p40 mutant gene which inhibits the secretion of IL-12p40 but normally secretes active IL-12p70 by making mutation at Asn-222 (human) or Asn-220 (mouse) amino acid of IL-12p40, which acts as a competitive inhibitor of active form of IL-12, IL-12p70. Therefore, the IL-12p40 mutant gene of the present invention can be useful for DNA vaccination and gene therapy against various diseases, for example, AIDS, hepatitis C or hepatitis B, cancer, influenza, tuberculosis and malaria, which essentially require cellular immune responses for their therapy.

Abstract: Novel NEOKINE polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length NEOKINE proteins, the invention further provides isolated NEOKINE fusion proteins, antigenic peptides and anti-NEOKINE antibodies. The invention also provides NEOKINE nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a NEOKINE gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides novel human transmembrane (NOVTRAN), neuromedin (NOVNEUR), gonadtropih (NOVGON), and interleukin-1 receptor antagonist (NOVINTRA A and B) proteins (NOVX proteins) and isolated nucleic acid molecules encoding the same. Also provided are antibodies that immunospecifically bind to NOVX polypeptides or polynucleotides, or derivatives, variants, mutants, or fragments thereof. The invention additionally provides methods in which a NOVX polypeptide, polynucleotide, and antibody are used in the detection, prevention, and treatment of a broad range of pathological states. Also provided are method of diagnosing and treating a lung disease associated with differential expression of human interleukin-1 epsilon.