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

Abstract: The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.

Abstract: The invention provides a ds-DNA oligomer which has from 25 to 150 base pairs, preferably 25 to 50 base pairs, and comprises the palindrome-containing sequence (one strand only shown) of formula (1): 5′B1. . . xN . . . B23′  (1) wherein B1 is ttgg or ccaa and B2 is correspondingly ccaa or ttgg and xN represents from 1 to 30 native nucleotides of substantially the native promoter sequence, together with the complementary strand, the oligomer being modified to make it resistant to degradation and denaturing in vivo. This oligomer or a vector carrying the palindrome-containing sequence (but not necessarily with the modification and not limited by any upper limit on the length of the oligomer sequence) can be used to inhibit transcription of the cytokine gene in vivo and is therefore useful in the therapy of diseases associated with undesired or excess production of cytokine.

Abstract: A protein belonging to the TNF superfamily called TRANCE involved in signal transduction, along with nucleic acids comprising DNA sequences and degenerate variants thereof which encode TRANCE are disclosed. Modulators which are TRANCE agonists and TRANCE antagonists are also disclosed, and can be used in pharmaceutical compositions and methods disclosed herein to modulate the active life of mature dendritic cells, T cell activation, and immune response in mammal.

Abstract: The invention relates to the discovery and characterization of several genes and the polypeptides they encode: thymotaxin (Tango-45), Tango-63d, Tango-63e, Tango-67, and huchordin (Tango-66). Thymotaxin is a new member of the C-C family of chemokines. Tango-63d and Tango-63e are two novel polypeptides within the tumor necrosis factor (TNF) receptor superfamily. Tango-67 is related to a number of growth factors, particularly members of the connective tissue growth factor family. Huchordin is related to chordin, a known protein that is involved in the induction of twinned axes, can completely rescue axial development in ventralized embryos, is a potent dorsalizing factor, and plays a crucial role in regulating cell-cell interactions in the organizing centers of head, trunk, and tail development.

Abstract: The present invention provides nucleotide and amino acid sequences that identify and encode novel expressed chemokines (PANEC-1 and PANEC-2) from human pancreas cells. The present invention also provides for antisense molecules to the nucleotide sequences which encode PANEC-1 and PANEC-2, expression vectors for the production of purified PANEC-1 and PANEC-2, antibodies capable of binding specifically to PANEC-1 and PANEC-2, hybridization probes or oligonucleotides for the detection of PANEC-1- or PANEC-2- encoding nucleotide sequences, genetically engineered host cells for the expression of PANEC-1 and PANEC-2, diagnostic tests for chemokine activation based on PANEC-1- and PANEC-2- encoding nucleic acid molecules and antibodies capable of binding specifically to the protein.

Abstract: The present invention relates to a polynucleotide in isolated form, which polynucleotide codes for a protein with the activity of the enzyme L-galactono-&ggr;-lactone dehydrogenase, which polynucleotide comprises at least the L-galactono-&ggr;-lactone dehydrogenase activity-determining parts of the coding part of the nucleotide sequence or a sequence derived therefrom on the basis of the degeneration of the genetic code. The invention further relates to the use of the polynucleotide in the production of transgenic plants, plant cells, or other eukaryotic cells.

Abstract: Human cytokine mixtures produced by cytokine regulatory factor-overexpressing cells and methods of production are disclosed. The mixtures are prepared by culturing human cytokine-producing cells under conditions of cytokine regulatory factor overexpression, treating the cells to induce cytokine production, and isolating the mixtures of cytokines produced by the cells.

Abstract: The present invention is directed to novel polypeptides having homology to members of the tumor necrosis factor receptor family 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.

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: 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: A tumor necrosis factor homolog, identified as DNA19355, is provided. DNA19355 polypeptide has apoptotic activity in mammalian cancer cells and may be involved in proinflammatory responses. Nucleic acid molecules encoding DNA19355, chimeric molecules and antibodies to DNA19355 are also provided.

Abstract: MUC1-specific binding members for cancer-associated MUC1 protein comprise a MUC1 binding domain, or portion thereof, for binding to an epitope of the protein core of MUC1. The MUC1-specific binding members comprise various antibody molecules and fragments thereof, including Fab antibodies; scFv antibodies; double scFv antibodies; diabodies; recombinant, full-length immunoglobulins; and immunocytokine fusion proteins; that are used in methods of diagnosing and treating cancer in various tissues, including breast, ovary, bladder, and lung, and in methods of purifying or isolating MUC1 protein. Polynucleotide molecules encoding MUC1-specific binding members, or portions thereof, are also described.

Abstract: A novel method of over expressing genes in plants is provided. This method is based on the RNA amplification properties of plus strand RNA viruses of plants. A chimeric multicistronic gene is constructed containing a plant promoter, viral replication origins, a viral movement protein gene, and one or more foreign genes under control of viral subgenomic promoters. Plants containing one or more of these recombinant RNA transcripts are inoculated with helper virus. In the presence of helper virus recombinant transcripts are replicated producing high levels of foreign gene RNA. Sequences are provided for the high level expression of the enzyme chloramphenicol acetyltransferase in tobacco plants by replicon RNA amplification with helper viruses and movement protein genes derived from the tobamovirus group.

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

Abstract: Mammalian Cystatin-8 (Zcys8) polypeptides, polynucleotides encoding the polypeptides, antibodies that specifically bind to the polypeptides, expression vectors comprised of the polynucleotides, and host cells transformed with the expression vectors.

Abstract: The invention provides methods for altering the expression profile of a cell to convert the cell from one cell type to a desired cell type. These reprogrammed cells may be used in a variety of medical applications for treating a mammal in need of a particular cell type.

Abstract: The invention is directed to purified and isolated novel ULBP polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above. ULBP polypeptide can be found on the surface of human B cell lymphomas. Mammalian forms of ULBP polypeptide in isolated or purified forms are provided. In addition, isolated nucleic acids encoding ULBP polypeptides and expression vectors comprising a cDNA encoding ULBP polypeptides are provided. The ULBP polypeptides can be isolated or synthesized and used to prepare antibodies, and in particular monoclonal antibodies, against the polypeptides. The antibodies, in turn, are useful for detecting the presence of ULBP polypeptides in human cell samples, which can be correlated with the existence of a malignant condition in a patient.

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. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

Abstract: A process for the production of a protein by cell culture, where the cells that produce the protein are cultured in the presence of a chemical agent that enhances the production of the protein.

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: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

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 provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

Abstract: The present invention relates to a novel hematopoietic signaling factor (HSF) protein which is a member of the cytokine superfamily. In particular, isolated nucleic acid molecules are provided encoding the human HSF protein. HSF polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same.

Abstract: The present invention relates to the identification of novel metallo-proteases (MP) in Gram-positive microorganisms. The present invention provides the nucleic acid and amino acid sequences for Bacillus (MP). The present invention also provides host cells having mutation or deletion of part or all of the gene encoding MP. The present invention also provides host cells further comprising nucleic acid encoding desired heterologous proteins such as enzymes. The present invention also provides cleaning compositions comprising an MP of the present invention.

Abstract: The invention provides improved methods of recombinant protein production in cell culture. More specifically, the invention relates to the activation of NF-kappa-B transcription factor complex in cells so as to improve production characteristics.

Abstract: The present invention relates to zalpha11 Ligand polynucleotide and polypeptide molecules. The zalpha11 Ligand is a novel cytokine. The polypeptides may be used within methods for stimulating the proliferation and/or development of hematopoietic cells in vitro and in vivo. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Abstract: A method of mobilizing hematopoietic stem cells from the bone marrow to the peripheral circulation is provided by administering to an animal an effective amount of mature, modified or multimeric forms of KC, gro&bgr;, gro&agr;, or gro&ggr;.

Abstract: The invention relates to NKAF II polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Abstract: Methods for improving purification and quantification of platelet derived growth factor (PDGF) proteins having structural heterogeneity are provided. Preparation of substantially pure isoforms of these proteins is achieved using TSK sulfopropyl cation exchange chromatography and reverse phase high performance liquid chromatography. A reverse charged capillary zone electrophoresis method enables quantification of substantially pure isoforms of these proteins resulting from endoproteolytic post-translational modifications. Compositions of the invention are substantially purified isoforms of secreted PDGF proteins having structural heterogeneity, more particularly purified intact, single-clipped, and double-clipped isoforms of recombinant PDGF-BB. Pharmaceutical compositions comprising at least one of these substantially purified recombinant PDGF isoforms and methods for their use in promoting wound healing are also provided.

Abstract: The present invention features a novel combination therapy useful in the treatment of autoimmune disease that increases or maintains the number of functional cells of a predetermined type in a mammal by killing or inactivating autoimmune cells and re-educating the host immune system.

Abstract: The present invention is directed to Bolekine polypeptides 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.

Abstract: Human chemotactic cytokine III 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, wound healing and psoriasis. 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, cerebral ischemia, glomerulonephritis, HTLV-1 related diseases 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: The invention relates to a novel tumor necrosis factor (TNF) homolog designated herein as TNF-related death ligand (TRDL). Isolated nucleic acid molecules are provided which encode TRDL. TRDL polypeptides are also provided, as are methods for identifying agonists and antagonists of TRDL activity.

Abstract: DNA sequences coding for a TNF-binding protein and for the TNF receptor of which this protein constitutes the soluble domain. The DNA sequences can be used for preparing recombinant DNA molecules in order to produce TNF-binding protein and TNF receptor. Recombinant TNF-binding protein is used in pharmaceutical preparations for treating indications in which TNF has a harmful effect. With the aid of the TNF receptor or fragments thereof or with the aid of suitable host organisms transformed with recombinant DNA molecules containing the DNA which codes for the TNF receptor or fragments or modifications thereof, it is possible to investigate substances for their interaction with the TNF receptor and/or for their effect on the biological activity of TNF.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Inhibition of eucaryotic pathogens and neoplasms and stimulation of lymphocytes and fibroblasts with lytic peptides such as cecropins and sarcotoxins. Eucaryotic cells are contacted with cecropin or sarcotoxin, or a synergistic combination of cecropins or sarcotoxin with lysozyme, in an amount effective to lyse or inhibit the cells. Target cells include eucaryotic microorganisms such as protozoa, e.g. T. cruzi and P. falciparum, mammalian lymphomas and leukemias, and cells infected with intracellular pathogens such as viruses, bacteria and protozoa. Also disclosed is a method for stimulating proliferation of lymphocytes and fibroblasts by contacting such cells with an effective amount of cecropin or sarcotoxin. The methods may be in vitro or in vivo.

Abstract: The present invention provides nucleic acid and amino acid sequence of the novel I-1 and I-2 polypeptides, which are associated with human inflammatory bowel disease (IBD). Methods of diagnosing and treating inflammatory bowel disease using the IBD-associated I-1 and I-2 antigens also are provided.

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: Macaca cynomolgus IL18 polypeptides and polynucleotides and method for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for screening for compounds which either agonize or antagonize Macaca cynomolgus IL18. Such compounds are expected to be useful in treatment of human diseases, including, but not limited to: cancer and auto-immune diseases.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 90% identical to residues 46-163 of SEQ ID NO:2 or residues 235-345 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

Abstract: Disclosed is the surprising discovery that a single amino acid provides the demarcation between the immunosuppressive and immunostimulatory properties of the cytokine, IL-10. The present invention thus provides mammalian and human IL-10 genes and polypeptides that have immunosuppressive properties, without immunostimulatory side-effects. Also provided are various methods of using the new IL-10 constructs, both in vitro and in vivo, particularly in sole or combination therapies involving immunosuppression, such as in the treatment of inflammatory diseases and disorders, and in transplantation.

Abstract: Method for the treatment of endotoxic shock in mammals. The use of vasoactive intestinal peptide (VIP) and peptide activating hypofissiary adenylate cyclase (PACAP) is described in the treatment of endotoxic shock in mammals. These substances inhibit the production of tumor necrosis factor (TNF) and interleukin 6 (IL-6).

Abstract: A recombinant first antigen, coupled with a foreign protein (such as immunoglobulin Fc from different species), can be used as a vaccine to induce active auto-immunity specifically through a T cell-dependent antibody response. The induced autoantibodies can recognize self-antigen in vivo and trigger immune responses to reduce or eliminate a target autologous antigen. Since there is evidence that the pathogenesis of some diseases, such as cancer, allergy, arthritis, atherosclerosis, graft rejection, or other inflammatory diseases, are caused by increased levels of certain autologous proteins, the instant compositions and methods provide a method of inducing autoantibodies to down-regulate the levels of a target autologous antigen or cells expressing the antigen to ameliorate diseases or disorders.

Abstract: Receptor components for IL-10 are isolated and characterized. The amino acid sequence and nucleic acid encoding various species variants of the receptors are disclosed. Uses of the purified receptor gene and polypeptide are disclosed, including means for screening for agonists and antagonists of the receptor ligands, for producing diagnostic or therapeutic reagents, and for producing antibodies. Therapeutic or diagnostic reagents and kits are also provided.

Abstract: The present invention provides a method of engrafting donor mammalian hematopoietic pluripotent cells in a mammalian recipient using a decreased amount of radiation, comprising: (a) administering to the recipient at least one dosage of a hematopoietic growth factor; (b) subjecting the recipient to a low dosage of radiation; and (c) transplanting the donor hematopoietic pluripotent cells in the recipient, thereby engrafting the donor mammalian hematopoietic pluripotent cells in the mammalian recipient using a decreased amount of radiation.

Abstract: The present invention relates to a novel retrovirus associated with autoimmune disease. The present invention provides nucleotide and amino acid sequences relating to GAG, PRO and POL proteins of the retrovirus as well as diagnostic techniques and antibodies for use in diagnosis. The retrovirus (HRV-5) according to the present invention has been detected in inflamed joints (RA, osteoarthritis (OA), reactive arthritis and psoriatic arthritis) but not normal synovium. Further, HRV-5 proviral DNA has been detected in blood from patients with RA and systemic lupus erythematosus (SLE).

Abstract: Chemokines are implicated in inflammation, ischemia and reperfusion injury, wound healing, allergies, as well as bacterial and viral pathogenesis. Moreover, chemokines may be involved in chronic diseases such as arthritis, asthma, and atherosclerosis. The present invention provides a new form of chemokine, designated as “Zchemo12.