Abstract: Attenuated recombinant viruses containing DNA coding for a cytokine and/or a tumor associated antigen, as well as methods and compositions employing the viruses, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least on of: human tumor necrosis factor; nuclear phosphoprotein p53, wildtype or mutant; human melanoma-associated antigen; IL-2; IFN&ggr;; IL-4; GNCSF; IL-12; B7; erb-B-2 and carcinoembryonic antigen. The recombinant viruses and gene products therefrom are useful for cancer therapy.

Abstract: The invention relates to a complex of specifically complex-forming proteins which are not naturally occurring, comprising the following components: a) at least one ligand specific for a target structure, b) at least one protein comprising a mutated dimerization domain, the mutated dimerization domain having been derived by mutation of a naturally occurring dimerization domain, it being possible for this mutated dimerization domain to interact specifically with component c) and the component b) being connected covalently to the component a), c) at least one protein comprising a mutated dimerization domain, the mutated dimerization domain having been derived by mutation of a naturally occurring dimerization domain, it being possible for this mutated dimerization domain to interact specifically with component b) and the component c) is linked covalently to the component d), and d) at least one effector.

Abstract: The present invention provides a method for the design and/or the selection of agonist or antagonist chemokine variants combining a phage display technology and a screening on living cells expressing the receptor of the corresponding native chemokine. It also provides RANTES variants having agonist properties towards said receptor, and methods for preventing and/or curing viral deseases.

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

Abstract: A method for cloning a nucleic acid fragment into a vector by flanking the fragment with first and second adapter sequences, and contacting the fragment with the vector having sequences homologous to the first and second adapter sequences under conditions such that the nucleic acid fragment is incorporated into the vector by homologous recombination in vivo in a host cell. Additionally, a method for selecting for a successful transformation of a vector by a nucleic acid insert. Also, systems for cloning a nucleic acid fragment into a vector without at least one of a restriction enzyme, a ligase, a gyrase, a single stranded DNA binding protein, or other DNA modifying enzymes. Further, a kit for cloning a nucleic acid fragment into a vector.

Abstract: A polypeptide containing a carrier peptide sequence and a plurality of epitope peptide sequences.

Abstract: The invention is directed to an isolated genomic polynucleotide sequence encoding interleukin-four induced protein as well as methods for obtaining said protein by expressing said polynucleotide sequences. The invention is also directed to constructs, vectors and hosts comprising such sequences, and oligonucleotide probes which hybridize to said polynucleotide sequences and kits comprising said probes. Additionally, the invention is directed to compositions comprising said polynucleotides and methods for using said compositions to treat, prevent or ameliorate pathological disorders, e.g., immune related disorders and novel methods of using the interleukin-four induced protein. The invention is also directed to methods for obtaining an antibody that binds to an epitope on said protein. The invention is further directed to a method for measuring the activity of said protein by measuring its L-amino acid oxidase activity.

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: The present application relates to a compositions comprising a compound which modulates the activity of T1-M protein, the use of compounds which modulate the activity of T1-M protein, and an in vitro method for influencing the proliferation and/or differentiation potential of bone cells.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: This invention provides methods and compositions for caspase-induced apoptosis. Chimeric proteins are provided that target cells in which apoptosis is to be induced. The chimeric proteins of this invention activate endogenous caspase or provide caspase units that cause cell death. Methods are provided for the use of the chimeric proteins of this invention for in vivo and ex vivo therapies to treat pathological conditions.

Abstract: The invention relates to methods of selecting proteins, out of large libraries, having desirable characteristics. Exemplified are methods of expressing enzymes and antibodies on the surface of host cells and selecting for desired activities. These methods have the advantage of speed and ease of operation when compared with current methods. They also provide, without additional cloning, a source of significant quantities of the protein of interest.

Abstract: Described herein are methods and compositions for the production and secretion of polypeptides. Included herein is the use of interrupting peptide transport activity for an increase in polypeptide production and/or secretion.

Abstract: Novel CC chemokines from human, reagents related thereto including purified proteins, specific antibodies and nucleic acids encoding these chemokines are provided. Also provided are methods of making and using said reagents and diagnostic kits.

Abstract: The present invention relates to Human Ck&bgr;-9 polypeptides and DNA (RNA) encoding such chemolcine polypeptides. Moreover, a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such Ck&bgr;-9 polypeptides for the treatment of leukemia, tumors, chronic infections, autoimmune diseases, fibrotic disorders, wound healing and psoriasis. Antagonists against such polypeptides and their use as a therapeutic agent to treat rheumatoid arthritis, autoimmune and chronic inflammatory and infective disease, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed. Diagnostic assays are also disclosed which detect the presence of mutations in the Ck&bgr;-9 coding sequence and over-expression of the Ck&bgr;-9 protein.

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 a process for preparing a cytokine inexpensively in large amounts by expressing the cytokine in a hen's egg using Sendai virus vector. The cytokine obtained by the present process is expected to be useful as medication because it has sugar chains very similar to those of mammals.

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: A novel CC chemokine which is from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding said chemokine. A chemokine receptor is also provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Control of mammalian gastro-intestinal tissues growth and repair is facilitated by the use of the proteins, making the proteins candidates for therapies.

Abstract: The invention is directed to chimeric polypeptides, e.g., bispecific antibodies, comprising a chemokine receptor binding domain and a T cell surface polypeptide or cell toxin binding domain, nucleic acids that encode them, and methods of making and using them. The chimeric polypeptides of the invention can include, be bound to, or attached to, a cell toxin. The invention is also directed to pharmaceutical compositions and methods for making and using them, including the treatment of immunological disorders, such as autoimmune diseases, and for the targeted elimination of cells, e.g., T lymphocytes and other cells latently infected with a primate immunodeficiency virus, such as a human immunodeficiency virus, e.g., HIV-1.

Abstract: A nucleic acid which can be used to express a polypeptide with interleukin-16 activity in a prokaryotic or eukaryotic host cell wherein the nucleic acid codes for a polypeptide with the amino acid sequence SEQ ID NO:2 or a SEQ ID NO:2 elongated N-terminally by an aspartic acid residue or a form shortened at the C-terminus by up to 8 amino acids, and is suitable for the production of an active IL-16 polypeptide.

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 present invention relates to novel human proteins designated Interleukin-21 (IL-21) and Interleukin-22 (IL-22), and isolated polynucleotides encoding these proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing these human proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human proteins.

Abstract: The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors 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 and other inflammatory diseases.

Abstract: A novel member of the heregulin superfamily has been identified which is designated “&ggr;-HRG”. This molecule, secreted by human breast cancer MDA-MB-175 cells, leads to the formation of a constitutive active receptor complex and stimulates the growth of these cells in an autocrine manner. &ggr;-HRG polypeptide and nucleic acid are disclosed, together with various uses therefor (e.g. use of &ggr;-HRG nucleic acid for the recombinant production of &ggr;-HRG). &ggr;-HRG antagonists (e.g. neutralizing antibodies and antisense nucleic acid molecules) as well as uses therefor are also described.

Abstract: Novel mammalian zcyto7 polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods including antibodies and anti-idiotypic antibodies.

Abstract: The present invention is directed to novel polypeptides designated herein as EG- VEGF 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. Also provided herein are methods of screening for modulators of EG-VEGF. Furthermore, methods and related methods of treatment are described herein which pertain to regulating cellular proliferation and chemotaxis.

Abstract: The present invention relates to deletion and substitution mutant polypeptides of human chemokine &bgr;-7 (Ck&bgr;-7), as well as nucleic acid molecules encoding such polypeptides and processes for producing such polypeptides using recombinant techniques. In one aspect, the invention also relates to uses of the full-length and mature forms of Ck&bgr;-7, as well as deletion and substitution mutants, in medical treatment regimens. In particular, the Ck&bgr;-7 polypeptides described herein may be employed to treat a variety of conditions, including rheumatoid arthritis, inflammation, respiratory diseases, allergy, and IgE-mediated allergic reactions.

Abstract: The invention relates to a complex of specifically complex-forming proteins which are not naturally occurring, comprising the following components: a) at least one ligand specific for a target structure, b) at least one protein comprising a mutated dimerization domain, the mutated dimerization domain having been derived by mutation of a naturally occurring dimerization domain, it being possible for this mutated dimerization domain to interact specifically with component c) and the component b) being connected covalently to the component a), c) at least one protein comprising a mutated dimerization domain, the mutated dimerization domain having been derived by mutation of a naturally occurring dimerization domain, it being possible for this mutated dimerization domain to interact specifically with component b) and the component c) is linked covalently to the component d), and d) at least one effector.

Abstract: The present invention relates to Neutrokine-alpha binding polypeptides (NAR). In particular, isolated nucleic acid molecules are provided encoding human NAR protein. NAR 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 NAR activity.

Abstract: LERK-5 polypeptides are disclosed, along with DNA sequences, vectors and transformed host cells useful in producing LERK-5. The LERK-5 polypeptides bind to elk and to hek, which are members of the eph/elk family of receptor tyrosine kinases.

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 lipopolysaccharide (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 invention provides methods of increasing yields of desired conformation of proteins. In particular embodiments, the invention includes contacting preparations of a recombinant protein with a reduction/oxidation coupling reagent for a time sufficient to increase the relative proportion of a desired configurational isomer.

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 MIP 1-&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: A method of enhancing viability of an oocyte by contacting the oocyte with a Wnt-4 polypeptide.

Abstract: There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human chemokine beta-11 (Ck beta-11) polypeptide and a human leukocyte adhesion inhibitor-1 (LAI-1) polypeptide (previously termed chemokine &agr;1(CK&agr;1 or cka-1), as well as Ck beta-11 and/or LAI-1 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same.

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: The present invention concerns a novel member of the tumor necrosis factor (TNF) family of cytokines. In particular, isolated nucleic acid molecules are provided encoding the endokine alpha protein. Endokine alpha polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic and therapeutic methods concerning TNF family-related disorders.

Abstract: A polyanionic polymer can improve the bioactivity and water-solubility properties of a drug to which it is joined. The inventive method provides a monodispersed preparation of a recombinantly-produced polyanionic polymer that can be easily manipulated, such as lengthened. An active moiety may be chemically or recombinantly joined to a polyanionic polymer to increase its biological half-life and/or solubility. The instant invention also provides a method for targeting the delivery of a polyanionic polymer conjugate or fusion protein to a specific cell type or tissue.

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: Human chemokine Alpha-2 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, autoimmune and chronic and acute inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever 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. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding the chemotactic cytokines and for detecting altered levels of the polypeptides in a host.

Abstract: Tumor suppressor genes play a major role in the pathogenesis of human lung cancer and other cancers. Cytogenetic and allelotyping studies of fresh tumor and tumor-derived cell lines showed that cytogenetic changes and allele loss on the short arm of chromosome 3 (3p) are most frequently involved in about 90% of small cell lung cancers and greater than 50% of non-small cell lung cancers. A group of recessive oncogenes, Fus1, 101F6, Gene 21 (NPRL2), Gene 26 (CACNA2D2), Luca 1 (HYAL1), Luca 2 (HYAL2), PL6, 123F2 (RaSSFI), SEM A3 and Beta* (BLU), as defined by homozygous deletions in lung cancers, have been located and isolated at 3p21.3.

Abstract: Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.

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: Purified genes encoding a cytokine or composite cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: The present invention provides new compositions and methods to induce therapeutic angiogenesis locally utilizing a collagen binding domain to target an angiogenesis modulating agents. Fusion polypeptides containing a collagen binding domain linked to an angiogenesis modulating agent are provided, as are nucleic acid sequences encoding the fusion polypeptides. Also included are methods for locally altering circulation by administering a fusion polypeptide consisting of a collagen binding domain linked to an angiogenesis modulating agent, or by administering a nucleic acid sequences encoding the fusion polypeptide. Tissue grafts in which isolated tissue is treated with a fusion polypeptide consisting of a collagen binding domain linked to an angiogenesis modulating agent, or with a nucleic acid sequences encoding the fusion polypeptide are also provided, as are methods of making the grafts.

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.