Abstract: The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain amino acid substitutions and may also have amino acid deletions at both the N- and C-termini. The invention also relates to pharmaceutical compositions containing the hIL-3 muteins and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the hIL-3 muteins, related microbial expression systems, and processes for making the hIL-3 muteins using the microbial expression systems. Included in the present invention are deletion mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus, and from 1 to 15 amino acids (a.a.119 to 133) have been deleted from the C-terminus, and which also contain amino acid substitutions in the polypeptide.

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: 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: This invention provides nucleic acid molecules encoding mutant human interleukin 13 molecules showing varying specificity for the restricted (IL4 independent) IL13 receptor. The mutant hIL13 molecules include those made by substituting the amino acid residues that occur in the alpha-helix regions of native hIL13 with various other amino acid residues. Some of the mutants retain the ability to bind and cause signaling through IL13 receptors, while other mutants do not.

Abstract: The present invention pertains to isolated DNA encoding avian interleukin-15 and to purified interleukin-15 polypeptides.

Abstract: The invention is directed to novel, purified and isolated IL-1 eta polypeptides and fragments thereof, the polynucleotides encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, peptides derived from these polypeptides, and uses thereof.

Abstract: A C to T DNA variation at position 3365 in exon 5 of the human Asthma Associated Factor 1 (AAF1) produces the predicted amino acid substitution of a methionine for a threonine at codon 117 of AAF1. When this substitution occurs in both alleles in one individual, it is associated with less evidence of atopic allergy including asthma, fewer abnormal skin test responses, and a lower serum total IgE. Thus, applicant has identified the existence of a non-asthmatic, non-atopic phenotype characterized by methionine at codon 117 when it occurs in both AAF1 gene products in one individual.

Abstract: Crystallographic and NMR solution structures of human IL-6 are reported. The invention provides models and systems incorporating such structures which are useful for identifying IL-6/IL-6 receptor interactions and for identification of agonists and antagonists of such interactions. Crystalline human IL-6 is also provided.

Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.

Abstract: Disclosed herein are mutant IL-15 polypeptides and methods for using these polypeptides to modulate the immune response in a patient.

Abstract: The present invention relates to canine interleukin-5 proteins; canine interleukin-5 nucleic acid molecules, including those that encode canine interleukin-5 proteins; to antibodies raised against such proteins; and to inhibitory compounds that regulate such proteins. The present invention also includes methods to identify and obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to regulate an immune response in an animal.

Abstract: This invention provides mutant hIL13 molecules include those made by substituting one or more of the amino acid residues that occur in the alpha-helix regions of native hIL13 with various other amino acid residues. Multiply mutated forms of hIL13 conjugated to cytotoxins are used to preferentially target diseased cells over non-diseased cells.

Abstract: The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

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: 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: 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: The present invention relates to the agonist properties of vMIP-I for the chemokine receptor CCR8 as expressed on Th2 cells. Methods of modulating a physiological signal specific to Th2 cells comprising contacting these cells with vMIP-I, agonists and antagonists thereof are disclosed. Methods for treating disease using CCR8 antagonists are also provided. The modulation of the Th2 cell populations through the vMIP-I/CCR8 interaction provides a new means for diagnosing and treating specific disease states and immunologic conditions.

Abstract: Activated lymphocytes derived from cord blood are excellently effective for preventing and treating various types of tumors and various types of infection. With interleukin 2 and/or anti-CD3 antibody, the lymphocytes derived from the cord blood is prepared by segregating lymphocytes from the cord blood and proliferating the segregated lymphocytes directly in vitro or segregating monocytes from cord blood and proliferating the monocytes in vitro. Also, the cord blood-derived activated lymphocytes can be effectively used for preventing recurrence of the diseases and promoting the take of stem cells or other organs.

Abstract: Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.

Abstract: The present invention provides novel nucleic acids isolated from a cDNA library for fetal liver-spleen tissue, and the novel polypeptide sequences encoded by these nucleic acids. These novel polynucleotide and polypeptide sequences were determined to be a novel Interleukin-3.

Abstract: A hybrid cytokine comprising the B-chain of hepatocyte growth factor and IL-7, linked by a linker molecule, having pre-pro-B growth stimulating activity.

Abstract: Methods are provided for improved production of hIL-3 either in glycosylated form from mammalian and yeast cells or in unglycosylated form from prokaryotes. Recombinantly produced human IL-3 is purified in a series of steps, initially employing hydrophobic interaction, followed by ion exchange chromatography and gel filtration.

Abstract: A soluble, heterodimeric interleukin 18 (IL-18) receptor molecule is described which comprises two subunits, one of which comprises an extracelluar domain, or a fragment thereof, of IL-18R, and the other of which comprises an extracelluar domain, or a fragment thereof, of AcPL. Preferably, the soluble, heterodimeric receptor binds to IL-18 with higher affinity than does either IL-18R or AcPL alone.

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: Rev-caspases comprising a primary product in which the small subunit is N-terminal to the large subunit are provided. Rev-caspases are used for screening and identifying caspase inhibitors and enhancers. Rev-caspase genes can be delivered to cells for gene therapy.

Abstract: Methods for promoting immunologic control of human immunodeficiency virus (HIV) in an HIV-infected subject are provided. The methods comprise administering to the subject highly active antiretroviral therapy (HAART) for at least one cycle of an intermittent dosing regimen in combination with administration of a pharmaceutical composition comprising a therapeutically effective amount of interleukin-2 (IL-2) or variant thereof. The combination of daily or intermittent administration of IL-2 (or variant thereof) and intermittent HAART promotes immunologic control of viral replication in the absence of HAART, thereby prolonging the length of time a patient may discontinue HAART before viral rebound necessitates further administration of HAART. Administration of IL-2 therapy in combination with an intermittent HAART dosing regimen provides an effective method for treating a subject infected with HIV.

Abstract: Rev-caspases comprising a primary product in which the small subunit is N-terminal to the large subunit are provided. Rev-caspases are used for screening and identifying caspase inhibitors and enhancers. Rev-caspase genes can be delivered to cells for gene therapy.

Abstract: The present invention provides novel nucleic acids encoding IL-1 Hy2, a novel member of the Interleukin-1 Receptor Antagonist family, the novel polypeptides encoded by these nucleic acids and uses of these and related products.

Abstract: The present invention relates to novel human IL-6-like polypeptides and isolated nucleic acids containing the coding regions of the genes encoding such polypeptides. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human IL-6-like polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human IL-6-like polypeptides.

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 relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) fused with other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

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

Abstract: IL-6 is produced via recombinant DNA techniques. The peptide is useful in the treatment of disorders characterized by deficiencies in hematopoietic cells and in combination with other hematopoietins in cancer therapies.

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 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 present invention provides novel nucleic acids, the novel polypeptide sequences encoded by these nucleic acids and uses thereof. These novel polynucleotide and polypeptide sequences were determined to be a novel Interleukin-1 Receptor Antagonist.

Abstract: The invention involves isolation of nucleic acid molecules, the expression of which are upregulated by interleukin-9. The amino acid sequences of the proteins which correspond to the nucleic acid molecules show some structural features of cytokines. In addition to the nucleic acid molecules and the proteins, various uses of the molecules are disclosed. The molecules are referred to as T cell inducible factors.

Abstract: A gene coded for a polypeptide which possesses interleukin-2 is isolated, and connected with a vector DNA which is capable of replicating in a procaryotic or eucaryotic cell at a position downstream of a promoter gene in the vector obtaining a recombant DNA, with which the cell is transformed to produce interleukin-2.

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 provides a method for chemically removing a N-terminal methionine residue selectively, specifically and efficiently from a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal. The method reacts a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal with an &agr;-diketone derivative, followed by hydrolysis.

Abstract: IL-6 is produced via recombinant DNA techniques. The peptide is useful in the treatment of disorders characterized by deficiencies in hematopoietic cells and in combination with other hematopoietins in cancer therapies.

Abstract: The present invention relates to a new IL-6 mutein, a DNA sequence coding for it, its use in therapy as well as a pharmaceutical composition comprising it. It is a potent IL-6 antagonist and can be advantageously used as a medicament in the treatment of diseases in which IL-6 has a pathogenetic action, such as, for example, plasmocytoma/myeloma, osteoporosis and neoplastic and auotoimmune diseases.

Abstract: A protein which induces the IFN-&ggr; production by immunocompetent cells and has a molecular weight of 19,000±5,000 daltons on SDS-PAGE or gel filtration method and a pI of 4.8±1.0 on chromatofocusing. The protein is isolated from mouse liver and can be purified by a monoclonal antibody specific to it. The monoclonal antibody can be also used for assaying the protein. Fragments of the protein can be used for production of antibodies, and can be produced recombinantly using appropriate medric acids, host cells and vectors. Fragments of nuclear acids may also be used as probes.

Abstract: Provided by the invention are novel methods, vectors and cells for the recombinant production of desired gene products. In particular, the invention relates to increased production of desired gene products by inducibly arresting cell proliferation. The invention also provides novel multicistronic expression vectors that are useful not only for recombinant gene expression, but also for other applications such as gene therapy, tissue engineering and metabolic engineering.

Abstract: The present invention relates generally to novel haemopoietin receptors, or components or parts thereof and to a method for cloning genetic sequences encoding same. More particularly, the subject invention is directed to recombinant or synthetic haemopoietin receptors or components or parts thereof. The receptor molecules or components or parts thereof and their genetic sequences of the present invention are useful in the development of a wide range of agonists, antagonists and therapeutics and diagnostic reagents based on ligand interaction with its receptor.

Abstract: A method for the high level production of active, properly processed recombinant protein in trans-splicing organisms is disclosed. The method involves the integration of the gene encoding the recombinant protein of interest into a chromosomal locus where it is transcribed under the direction of the rRNA promoter. The gene is also operably linked to intergenic regions allowing the protein to be translated in these organisms. The recombinant organisms expressing a therapeutic protein can also be used to treat a disease or undesirable condition which is characterized by a deficiency in that protein.

Abstract: The invention relates to the cloning of the human interleukin-1&agr; gene, its engineering into suitable expression vectors, hosts transformed with such expression vectors, and production of biologically active recombinant human interleukin-1&agr;.

Abstract: A method of providing a patient with an enhanced immune response is disclosed. In one embodiment, the method comprises the step of vaccinating the patient with a vaccine comprising a combination of DNA encoding interleukin-6 and DNA encoding an antigen capable of enlisting an enhanced immune response in a patient. In one embodiment, the enhanced immune response is a therapeutic response. In another embodiment, the enhanced immune response is a protective immune response.

Abstract: Novel recombinant yeasts are disclosed which are highly stable in a complex medium. Said yeasts are of the Kluyveromyces genus in which an essential gene is nonfunctional, containing a vector bearing a functional copy of said gene.