Abstract: Four novel members of the EPH sub-family of receptor protein tyrosine kinases are disclosed. Nucleic acid sequences encoding receptor proteins, recombinant plasmids and host cells for expression, and methods of producing and using such receptors are also disclosed.

Abstract: Isolated and purified chemokine peptides, variants, and derivatives thereof, as well as chemokine peptide analogs, are provided.

Abstract: The present invention relates to a novel CK?-6 protein which is a member of the alpha chemokine family. In particular, isolated nucleic acid molecules are provided encoding the human CK?-6 protein. CK?-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?-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 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: Disclosed are novel multi-functional chimeric hematopoietic receptor agonist proteins, DNAs which encode the multi-functional chimeric hematopoietic receptor agonist proteins, methods of making the multi-functional chimeric hematopoietic receptor agonist proetiens and methods of using the multi-functional chimeric hematopoietic receptor agonist proteins.

Abstract: The invention provides methods and materials for evaluating cardiovascular conditions (e.g., angina conditions). Specifically, the invention provides methods and materials related to determining whether or not a mammal has at least one unstable plaque. The invention also provides kits for assessing cardiovascular conditions, substantially pure populations of cells, and methods of identifying compounds to treat life-threatening cardiovascular conditions (e.g., unstable angina).

Abstract: The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.

Abstract: A therapeutic agent for the treatment of septicemia, its preparation and use, with application in the pharmaceutical industry and medicine. This therapeutic agent contains essential element, the lipopolysaccharide binding protein (LBP). Also disclosed are LBP variants, mutants and hybrid proteins. Murine or rabbit LBP may also be used, besides human LBP.

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 present invention relates to granulocyte colony stimulating factor (“G-CSF”) analog polypeptide compositions, related nucleic acids, expression constructs, host cells, and processes for recombinant production of the present G-CSF analogs. The concept detailed herein involves novel mutants of G-CSF, using single substitutions to amino acids, which were rationally chosen to affect the cellular trafficking of G-CSF and/or G-CSFR. In addition, pharmaceutical compositions, and methods of use are provided.

Abstract: We have discovered that growth hormones from ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.

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 DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.

Abstract: A method is provided for transforming Brassica plants to express DNA sequences of interest from the plant cell plastid. The method allows the transformation of Brassica plant tissue with heterologous DNA constructs. Such DNA constructs comprise, in the 5? to 3? direction of transcription, a promoter region functional in a plant plastid and a DNA sequence of interest. The invention further provides for Brassica cells in which the plastids contain heterologous DNA constructs.

Abstract: The present invention relates to a fusion polypeptide which comprises a polypeptide having G-CSF activity and a polypeptide having TPO activity and DNA which codes for the fusion polypeptide, to a fusion polypeptide in which a polypeptide having G-CSF activity and a polypeptide having TPO activity are fused via a spacer peptide and DNA which codes for the fusion polypeptide and to a polypeptide in which the fusion polypeptide comprising a polypeptide having G-CSF activity and a polypeptide having TPO activity is chemically modified with a polyalkylene glycol derivative. It also relates to an anemia-treating composition containing the fusion polypeptide as an active ingredient.

Abstract: The present application is directed to the discovery that hedgehog gene products are able to protect peripheral nerve cells under conditions which otherwise result in peripheral neuropathy. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, or other molecules which regulate patched or smoothened signalling, and their uses as protective agents against both acquired and hereditary neuropathies. As used herein, “peripheral neuropathy” refers to a disorder affecting a segment of the peripheral nervous system. For instance, the method of the present invention can be used as part of a treatment program in the management of neuropathies associated with systemic disease, e.g., viral infections, diabetes, inflamation; as well as genetically acquired (hereditary) neuropathies, e.g., Charcot-Marie-Tooth disease; and neuropathies caused by a toxic agent, e.g., a chemotherapeutic agent such as vincristine.

Abstract: Polypeptide and polynucleotide vaccines effective to treat or prevent infection of a mammal, such as a dog, a cat, or a human, by a protozoan. Methods of treatment and prevention are also provided, including therapeutic administration of the vaccine to an infected mammal to prevent progression of infection to a chronic debilitating disease state. Preferred embodiments of the polynucleotide vaccine contain nucleotide coding regions that encode polypeptides that are surface-associated or secreted by T. cruzi. Optionally the efficacy of the polynucleotide vaccine is increased by inclusion of a nucleotide coding region encoding a cytokine. Preferred embodiments of the polypeptide vaccine include immunogenic peptides that contain membrane transducing sequences that allow the polypeptides to translocate across a mammalian cell membrane.

Abstract: The present invention provides an agent for treating retinopathy containing a tricyclo compound of formula (I)

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: This invention pertains to BIV constructs encompassing BIV combination vectors, BIV vectors and BIV packaging vectors and particularly the invention pertains to a three vector system comprising: a) a BIV vector construct including a DNA segment from a BIV genome, a packaging sequence to package RNA into virions; a promoter operably linked to the DNA segment; and a transgene operably linked to a second promoter; b) a BIV packaging vector construct comprising a BIV DNA sequence fragment comprising at least a gag gene or pol gene of BIV; a promoter operably linked to the BIV DNA fragment; and a polyadenylation sequence located downstream of the BIV DNA fragment; and c) an expression vector construct comprising a gene encoding a viral surface protein. Also provided is a method for transferring a gene of interest into a mammalian cell.

Abstract: The present invention relates to a novel human protein called Cytokine Receptor Common Gamma Chain Like, and isolated polynucleotides encoding this protein. Also provided are vectors, host cells, antibodies, and recombinant methods for producing this human protein. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to this novel human protein.

Abstract: Isolated ligands, DNAs encoding such ligands, and pharmaceutical compositions made therefrom, are disclosed. The isolated ligands can be used to regulate an immune response. The ligands are also useful in screening for inhibitors thereof.

Abstract: Fc fusion proteins of human G-CSF with increased biological activities relative to rhG-CSF on a molar basis are disclosed. The hG-CSF-L-vFc fusion protein comprises hG-CSF, a flexible peptide linker of about 20 or fewer amino acids, and a human IgG Fc variant. The Fc variant is of a non-lytic nature and shows minimal undesirable Fc-mediated side effects. A method is also disclosed to make or produce such fusion proteins at high expression levels. Such hG-CSF-L-vFc fusion proteins exhibit extended serum half-life and increased biological activities, leading to improved pharmacokinetics and pharmacodynamics, thus fewer injections will be needed within a period of time.

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

Abstract: Nucleic acid compositions and methods of use in treating solid tumors are disclosed. The nucleic acid compositions include a plurality of nucleic acid plasmids. Each plasmid encodes a single protein, either a cytokine or an anti-tumor protein. Each composition includes a plurality of these nucleic acid plasmids that encode a combination of two or more cytokines, a combination of cytokines and anti-tumor proteins, a combination of anti-tumor proteins, or an anti-tumor protein. The nucleic acid compositions of the invention can be delivered locally to a solid tumor.

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 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 diseases, as well as clues for preventing and/or curing inflammatory or malignant diseases.

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: The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF&agr;). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF&agr; variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

Abstract: The present invention relates to at least one novel Mut-IL-13 proteins, antibodies, including isolated nucleic acids that encode at least one Mut-IL-13 protein or antibody, Mut-IL-13 vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention relates to canine and feline proteins. In particular, the present invention discloses feline interleukin-18, feline caspase-1, feline interleukin-12 single chain and canine interleukin-12 single chain proteins. The present invention also includes feline interleukin-18, feline caspase-1, feline interleukin-12 single chain and canine interleukin-12 single chain nucleic acid molecules encoding such proteins, antibodies raised against such proteins and/or inhibitors of such proteins or nucleic acid molecules. The present invention also includes therapeutic compositions comprising such nucleic acid molecules, proteins, antibodies and/or inhibitors, as well as their use to evaluate and regulate an immune response in an animal.

Abstract: The invention is directed to novel, purified and isolated IL-1 zeta and Xrec2 polypeptides and fragments thereof, 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 uses thereof.

Abstract: This invention is directed to sequences that are involved in the molecular pathways of tumor suppression, tumor reversion, apoptosis and/or virus resistance. The use of the compounds having these sequences, or encoded by them, in treating cancer, neurodegenerative diseases or viral diseases, and screening methods for compounds having such therapeutic properties are also encompassed.

Abstract: The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g., be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g., be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate has one or more improved properties such as increased biological half-life and reduced side effects.

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: The present invention relates to the solubilization and recovery in high yield, of inclusion body proteins from host cells using an appropriate denaturating agent. The process avoids the use of high concentration of chaotropic agents such as guanidine hydrochloride or urea.

Abstract: The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. Said oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membranous signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence.

Abstract: A modified human granulocyte-colony stimulating factor(hG-CSF) is produced by culturing a microorganism transformed with an expression vector comprising a gene encoding a modified hG-CSF to produce and secrete the modified hG-CSF to periplasm, said modified hG-CSF being obtained by replacing at least one of the 1st, 2nd, 3rd and 17th amino acids of wild-type hG-CSF(SEQ ID NO: 2) with other amino acid

Abstract: The invention provides molecules containing nucleic acid sequences for fragments of LPS-induced TNF-&agr; factor (LITAF) and vectors containing these sequences. Also provided are molecules that contain the peptide sequence SQTWREPGAAGSPFHL, or homologs thereof. Such molecules may be useful in the treatment of diseases that relate to the expression of TNF-&agr;, where treatment involves the modulation of this expression. The invention also provides methods for identifying compounds that inhibit or enhance the transcription of TNF-&agr;.

Abstract: There are disclosed therapeutic compositions and methods using a human monocyte-colony inhibitory factor (M-CIF) polypeptide (previously termed MIP1-&ggr; chemokine &bgr;1(CK&bgr;1 or ckb-1)), as well as ioslated nucleic acid molecules encoding M-CIF, and vectors, host cells and recombinant methods for producing the same.

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 agonists and antagonists of Neutrokine-alpha and/or Neutrokine-alphaSV activity. Also 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: A novel CC chemokine which is from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding said chemokine. Methods of using said reagents and diagnostic kits are also provided.

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

Abstract: The present invention concerns a process by which a misfold in an Fc fusion molecule can be prevented or corrected. In one embodiment, the process comprises (a) preparing a pharmacologically active compound comprising an Fc domain; (b) treating the fusion molecule with a copper (II) halide; and (c) isolating the treated fusion molecule. The pharmacologically active compound can be an antibody or a fusion molecule comprising a pharmacologically active domain and an Fc domain. The preferred copper (II) halide is CuCl2. The preferred concentration thereof is at least about 10 mM for fusion molecules prepared in E. coli; at least about 30 mM for fusion molecules prepared in CHO cells. The process can be employed with any number of pharmacologically active domains. Preferred pharmacologically active domains include OPG proteins, leptin proteins, soluble portions of TNF receptors (e.g., wherein the fusion molecule is etanercept), IL-1ra proteins, and TPO-mimetic peptides.

Abstract: A cell culture preparation and methods are provided which are suitable for production in cells of a first protein in a class of proteins where the medium is deficient in a second protein in a related class, where the second protein is normally present in the serum and capable of interfering with the purification of the first compound.

Abstract: The invention relates to human cytokine 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: Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Disclosed herein are therapeutic compositions containing agents that modulate the immune response in a patient.

Abstract: The invention relates to polypeptides which exert the biological activity of GABA B receptors, and to nucleic acids which encode these polypeptides, and in particular to their use for finding active compounds for crop protection.

Abstract: An isolated novel type CC chemokine-like protein which is expressed from peripheral blood mononuclear cells under an immunological stimulus and has a cell migration activity; a DNA encoding the protein; an expression vector and a transformant containing the DNA; a process for producing a recombinant protein by using the transformant; and a pharmaceutical composition containing the protein.