Abstract: Human TNF-gamma-alpha and TNF-gamma-beta polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides to inhibit cellular growth, for example in a tumor or cancer, for facilitating wound-healing, to provide resistance against infection, induce inflammatory acitvities, and stimulating the growth of certain cell types to treat diseases, for example restenosis. Also disclosed are diagnostic methods for detecting a mutation in the TNF-gamma-alpha and TNF-gamma-beta nucleic acid sequences or overexperession of the TNF-gamma-alpha and TNF-gamma-beta polypeptides. Antagonists against such polypeptides and their use as a therapeutic to treat cachexia, septic shock, cerebral malaria, inflammation, arthritis and graft-rejection are also disclosed.

Abstract: The present invention provides to polynucleotides and secreted proteins encoded by the polynucleotides. The proteins include and cytokines, growth factors, include fusion proteins operably linked to a second polypeptide. The invention further provides therapeutic and diagnostic methods utilizing the polynucleotides, polypeptides, and antagonists of the polypeptides.

Abstract: The invention relates to the method of preventing and treating sepsis using chemokines selected from mature or modified KC [SEQ ID NO: 1], gro&agr;[SEQ ID NO:2], gro&bgr;[SEQ ID NO: 3] or gro&ggr;[SEQ ID NO: 4] or multimers thereof, alone or in conjunction with an anti-infective agent. This invention also relates to a new gro&bgr; dimer chemokine.

Abstract: Disclosed are nucleic acid sequences, for example, DNA or RNA sequences, which encode an immunoglobulin Fc-Interferon-alpha fusion protein. The nucleic acid sequences can be inserted into a suitable expression vector and expressed in mammalian cells. Also disclosed is a family of immunoglobulin Fc-Interferon-alpha fusion proteins that can be produced by expression of such nucleic acid sequences. Also disclosed are methods of using such nucleic acid sequences and/or fusion proteins for treating conditions, for example, hepatitis, which are alleviated by the administration of interferon-alpha.

Abstract: Human chemokine Alpha-3 polypeptides and DNA (RNA) encoding such chemotactic cytokines and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemotactic cytokines for the treatment of leukemia, tumors, chronic infections, auto-immune disease, fibrotic disorders, sepsis, wound healing and psoriasis and to stimulate stem cell mobilization. Antagonists against such chemotactic cytokines and their use as a therapeutic to treat rheumatoid arthritis, auto-immune and chronic and acute inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever, ARDS and bone marrow failure are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides.

Abstract: There is disclosed a polypeptide (CD40-L) and DNA sequences, vectors and transformed host cells useful in providing CD40-L polypeptides. More particularly, this invention provides isolated human and murine CD40-L polypeptides that bind to the extracellular binding region of a CD40 receptor.

Abstract: Novel cytokine polypeptides, materials and methods for making them, and method of use are disclosed. The polypeptides comprise at least nine contiguous amino acid residues of SEQ ID NO:2 or SEQ ID NO:4, and may be prepared as polypeptide fusions comprise heterologous sequences, such as affinity tags. The polypeptides and polynucleotides encoding them may be used within a variety of therapeutic, diagnostic, and research applications.

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 present invention relates to the use of polypeptides of the MIP (macrophage inflammatory proteins) class for the treatment of diseases involving a pathological change of thrombocytopolesis, especially for the treatment of thrombocytopenia.

Abstract: The present invention relates to a novel Neutrokine-alpha, and a splice variant thereof designated Neutrokine-alphaSV, polynucleotides and polypeptides which are members of the TNF family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV 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-alpha and/or Neutrokine-alphaSV activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: The invention provides a novel protein, PX3.101, which can be isolated from honey bee venom, antibodies against the polypeptide and nucleic acids encoding PX3.101 and fragments thereof. The invention also provides pharmaceutical compositions based upon PX3.101 polypeptide and methods for using same in the treatment of various diseases, including various inflammatory diseases such as rheumatoid arthritis.

Abstract: The present invention relates to a novel CK&agr;-5 protein which is a member of the alpha chemokine family. In particular, isolated nucleic acid molecules are provided encoding the human CK&agr;-5 protein. CK&agr;-5 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 CK&agr;-5 activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: This invention concerns a method of producing human granulocyte colony-stimulating factor (hGCSF) and human growth hormone (hGH) from least by using recombinant DNA technology. More specifically, this invention relates to a method of producing hGCSF or hGH by using yeast expression vector which contains: hybrid promoters comprising promoters of two different yeast-derived genes, yeast killer toxin leader peptide, and amino terminus of IL-1&bgr;. In addition, this invention relates to a method of producing hGCSF by using expression vector which contains promoter and secretion signal of HSP 150.

Abstract: Human chemokine Beta-10 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 a novel CK&bgr;-13 protein which is a member of the chemokine family. In particular, isolated nucleic acid molecules are provided encoding the human CK&bgr;-13 protein. CK&bgr;-13 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 CKCK&bgr;-13 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 is directed to an Immunodeficiency-virus Suppressing Lymphokine (ISL) produced by stimulated CD8+ PBMC, cloning and isolation of nucleic acid molecules for eukaryotic ISL, and methods of treating viral infections with ISL. ISL is able to suppress the replication of viruses, especially retroviruses, in vitro and in vivo. More, specifically, a method is described for detecting a compound capable of inducing the expression of ISL by measuring the presence of ISL and the ability of ISL to inhibit HIV transcription.

Abstract: Novel Analogues of Monocyte Chemoattractant Protein-1 (MCP-1) have substitution of an alanine, glycine or threonine for the natural valine in position 9 of MCP-1 (9-76).

Abstract: Methods are disclosed for refolding proteins of the TGF-&bgr; family of proteins. The methods employ as refolding agents one or more compounds which are non-detergent zwitterionic compounds, such as sulfobetaines, substituted pyridines, substituted pyrroles and acid substituted aminocyclohexanes.

Abstract: The present invention is directed to novel polypeptides having sequence identity with IL-17 and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders.

Abstract: Human chemokine &bgr;-6 agonist and antagonist polypeptides and DNA encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. The chemokine &bgr;-6 antagonists of the present invention may be employed to treat rheumatoid arthritis, lung inflammation, allergy, asmtha, infectious diseases and to prevent inflammation and atherosclerosis. The chemokine &bgr;-6 agonists may be employed to myeloprotect patients undergoing chemotherapy.

Abstract: An isolated, synthetic preparation of a novel neutrophil-specific chemotactic factor (NCF), monoclonal antibodies having specific binding affinity of NCF and a clone containing the complete cDNA coding sequence for NCF are disclosed.

Abstract: Novel receptor polypeptides, polynucleotides encoding the polypeptides, and related compositions. The polypeptides of the present invention can be used to down-regulate their natural ligands. The polynucleotides and subsequences thereof can be used as diagnostic probes to determine if chromosome 19 is mutated. The antibodies which bind to the polypeptides can be used to purify the receptors and to inhibit the binding of the ligands onto the receptors.

Abstract: The present invention relates to a novel CK(&agr;-6 protein which is a member of the alpha chemokine family. In particular, isolated nucleic acid molecules are provided encoding the human CK&agr;-6 protein. CK&agr;-6 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 CK&agr;-6 activity. Also provided are diagnostic methods for detecting CNS and immune system-related disorders and therapeutic methods for treating CNS and immune system-related disorders.

Abstract: The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with a other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

Abstract: The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

Abstract: A E. coli recombinant plasmid expressing a fusion protein having the human erythropoietin receptor extracellular domain is disclosed. A purified fusion protein produced from such a vector is also disclosed, the fusion protein having a cleavage site suitable for separating the erythropoietin receptor extracellular domain from the remainder of the fusion protein. Antibodies having specific binding affinity for a purified extracellular domain polypeptide are also disclosed. The purified human erythropoietin receptor fragment polypeptide binds erythropoietin. The articles, compositions and methods of the invention are useful for studying ligand binding to erythropoietin receptor and for quantitating the amounts of erythropoietin receptor, as well as for understanding receptor structure and signal transduction.

Abstract: This invention provides a novel polypeptide useful in the field of medicines, a novel DNA which encodes the novel polypeptide, a recombinant DNA molecule which contains the novel DNA, a transformant transformed with the novel DNA or the recombinant DNA molecule, a process for the purification of the novel polypeptide, a process for the production of the novel polypeptide, an antibody which recognize the novel polypeptide, an oligonucleotide complementary to the novel DNA and a novel screening method. Particularly this invention provides a novel polypeptide which is Fas ligand or a fragment thereof. This novel polypeptide can be used as an effective ingredient of a medicament for regulating the apoptosis in a living body. This novel polypeptide is obtained by identifying a DNA fragment which encodes the novel polpeptide, transforming a desired host with a recombinant DNA molecule which contains the DNA fragment and purifying the novel polypeptide produced by the resulting transformant.

Abstract: The present invention concerns a member of the human chemokine CC protein family. In particular, isolated nucleic acid molecules are provided encoding the chemokine &bgr;-15 protein. Chemokine &bgr;-15 polypeptides are also provided. The invention further concerns diagnostic methods for detecting thymus disorders and therapeutic methods for modulating bone marrow cell proliferation and differentiation.

Abstract: The invention relates to the use of IL-15 or active variants thereof and/or IL-15 activity enhancing compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system, such as manipulating viability ad/or responsiveness of said memory cells. The IL-15 activity enhancing compound is for example lipopolysaccharidc (LPS). The invention further relates to the use of IL-15 inhibiting or eliminating compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system. Such inhibiting or eliminating compounds are for example anti-IL-15 antibodies, anti-IL-15R&agr; antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15R&agr;, fusion proteins consisting of soluble IL-15R&agr;, and Fc fragment, compounds, e.g. peptides, binding and/or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.

Abstract: The present invention provides novel polynucleotides encoding Drosophila DmTNF polypeptides, fragments and homologs thereof. The present invention also is directed to novel polynucleotides encoding two Drosophila DmTNF variants, DmTNFv1 and DmTNFv2 polypeptides, fragments and homologs thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, in addition to methods of genetically modifying Drosophila or cultured cells to express or mis-express DmTNF, DmTNFv1, or DmTNFv2. The invention also relates to the use of such modified insects or cells to characterize DmTNF activity, identify TNF-like genes and/or genes implicated in modulating TNF, characterize TNF signaling pathways, and/or to identify modulators of DmTNF activity.

Abstract: The invention relates to a method for forming a mixed disulfide of recombinant proteins, by solubilizing with a denaturing agent in the presence of a disulphide component, and then adding a disulphide component plus a denaturing agent, at a concentration sufficient to form a mixed disulfide.

Abstract: Hek ligand (hek-L) polypeptides as well as DNA sequences, vectors and transformed host cells useful in providing hek-L polypeptides. The hek-L polypeptides bind to a cell surface receptor (hek) that is a member of the receptor tyrosine kinase family. Hek is expressed on cells that include certain tumor cell lines. The hek-L polypeptides also bind a distinct receptor tyrosine kinase known elk.

Abstract: The invention relates to novel proteins with TNF-&agr; antagonist activity and nucleic acids encoding these proteins. The invention further relates to the use of the novel proteins in the treatment of TNF-&agr; related disorders, such as rheumatoid arthritis.

Abstract: Novel polypeptides of the truncated form of human Ck&bgr;-8 are provided. Methods for using the polypeptides are also provided.

Abstract: A nucleic acid with which expression of a polypeptide having interleukin-16 activity can be achieved or regulated in a prokaryotic or eukaryotic host cell, wherein in the region coding for the polypeptide, the nucleic acid (1) corresponds to the DNA sequence SEQ ID NOS:1 and 5-7 or its complementary strand; (b) hybridizes under stringent conditions with the DNA of sequence SEQ ID NOS:1 and 5-7; (c) or is a nucleic acid sequence which, if there was no degeneracy of the genetic code, would hybridize under stringent conditions with the nucleic acid sequences defined by (a) and (b); (d) and, if it codes for a polypeptide having interleukin-16 activity, is suitable as genomic DNA for the recombinant production of IL-16 in eukaryotic host cells and processes for producing the same and pharmaceutical compositions containing the same.

Abstract: Fusion proteins comprising a variant form of TGF-beta Type II receptor linked to a portion of an immunoglobulin constant chain are described. Also described are methods of using the fusion proteins of the invention to treat a variety of fibroproliferative disorders.

Abstract: The present invention provides soluble CD39 polypeptides and compositions, and methods for inhibiting platelet activation and recruitment in a mammal comprising administering a soluble CD39 polypeptide.

Abstract: The present invention provides chemokine-like factor (CKLF) polypeptides with chemotactic and hematopoietic stimulating activities and polynucleotides encoding such polypeptides. Additionally, a method for producing such CKLF polypeptides by recombinant techniques is provided. Also provided are the antibodies and antagonists against such polypeptides. The present invention further disclose a drug compound comprising a therapeutically effective amount of such CKLF polypeptides as well as pharmaceutically acceptable excipients and carriers. Also disclosed are the uses of such CKLF polypeptides and polynucleotides in diagnostics or therapeutics to treat immunodeficiency, hematopoietic diseases and primary tumors.

Abstract: A method for the culture of hematopoietic cells and/or production of human cytokines using immortalized human stromal cell lines is provided. These immortalized stromal cell lines condition media such that the ability of the hematopoietic stem cells to self-replicate and/or differentiate is maintained by the media or the ability of the committed progenitors to expand and/or differentiate is maintained by the media. Further provided are irradiated and non-irradiated immortalized human stromal cells that synthesize cytokines, such as, IL-7, IL-8, IL-11, FLT3L, SCF, LIF, M-CSF, TGF-beta 1, GM-CSF, MIP-1alpha, G-CSF, and MCP-1.

Abstract: The present invention provides novel human cytokines (designated individually as NHC-1 and NHC-2, and collectively as NHC) and polynucleotides which identify and encode NHC. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding NHC and a method for producing NHC. The invention also provides for use of NHC and agonists, antibodies, or antagonists specifically binding NHC, in the prevention and treatment of diseases associated with expression of NHC. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding NHC for the treatment of diseases associated with the expression of NHC. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding NHC.

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 use of the IL-4 receptor for the therapy, prophylaxis and diagnosis of allergic, viral, parasitic and bacterial diseases and of fungal infections. The invention relates to the use of the IL-4 receptor or of derivatives thereof for the therapy, prophylaxis and diagnosis of allergic, viral, parasitic and bacterial diseases and of fungal infections.

Abstract: Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

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: Methods for stimulating erythropoiesis using the hematopoietic protein thrombopoietin, optionally in combination with erythropoietin, are provided. The methods provided may be used to stimulate erythropoiesis in bone marrow and peripheral blood cells and in vitro and in vivo. In addition, methods for treatment of thrombocytopenia and anemia in patients are disclosed.

Abstract: Novel polynucleotides and the proteins encoded thereby are disclosed.

Abstract: A bovine- or human-derived calcium-binding protein with a prescribed amino acid sequence, a method for its production, and antibodies against the protein and uses thereof.

Abstract: The present invention provides methods for inhibiting the growth of selected tumors utilizing recombinant viral vectors. Briefly, within one aspect of the present invention, a method for inhibiting the growth of a selected tumor is provided comprising the step of directly administering to a warm-blooded animal a vector construct which directs the expression of at least one anti-tumor agent, such that the growth of said tumor is inhibited. Representative examples of anti-tumor agents include immune activators and tumor proliferation inhibitors.

Abstract: The present invention relates to compositions and methods for enhanced cytokine production in human cell culture, particularly under conditions where apoptotic cell death is suppressed by expression of CrmA.

Abstract: The invention is directed to LERK-6 as a purified and isolated protein, the DNA encoding the LERK-6, host cells transfected with cDNAs encoding LERK-6.