Abstract: Disclosed are compositions and methods useful in the regulation of cell proliferation. The invention provides TGF-? (transforming growth factor ?) and IGFBP-3 (insulin like growth factor binding protein 3) as ligands that engage LRP (low density lipoprotein receptor-related protein), heretofore known as T?R-V (TGF-? receptor V) and IGFBP-3 receptor, to effect a change in the phosphorylation and activation status of IRS (insulin receptor substrate) proteins. Compositions comprising TGF-? or IGFBP-3 and LRP or IRS protein are useful in the inhibition of cell proliferation and in the treatment of various diseases associated with unregulated cell proliferation.

Abstract: The present invention provides a purified polynucleotide encoding a novel polypeptide, designated Fhm, which belongs to the TNF gene superfamily; to purified Fhm polypeptide molecules; to antibodies that bind Fhm; to materials comprising such molecules; and to methods of using such molecules.

Abstract: The present invention provides a method for screening a cytostatic agent characterized by determining an effect of inhibiting intracellular signaling mediated by a remaining fragment of a cell membrane-anchored growth factor, and the cytostatic agent. In growth factors of the EGF family, the physiological significance of the remaining fragment is clarified, and a method for controlling its action is searched, and thus a novel pharmaceutical can be provided.

Abstract: For the effective treatment of diseases such as cancer in which hIGF participates, there have been desired to be developed antibodies which strongly bind to both factors hIGF-I and hIGF-II and inhibit their functions and fragments of these antibodies. The present invention provides antibodies which have the ability to specifically bind to human IGF-I and IGF-II to thereby inhibit the functions of human IGF-I and IGF-II and have binding activity with a binding constant of 5×109 M?1 or more measured with a biosensor BIACORE. In addition, the present invention provides diagnostics, preventives and remedies for an hIGF-mediated disease and a disease showing pathological progressing due to abnormally promoted hIGF production, which use said antibodies.

Abstract: This invention relates to the use of the IL-2 common gamma chain (c?c) and related molecules for the modulation of signal activities controlled by NIK, and some new such molecules.

Abstract: Mutants of CC chemokines, which contain at least two mutations in the cationic site of the 40's loop and which, relative to the wild-type molecule, have a reduced GAG-binding activity. In particular it has been found that such mutated chemokines are effective in the treatment of multiple sclerosis and/or demyelinating diseases. A triple mutant of RANTES is the compound showing the best results.

Abstract: The invention relates to isolated complexes comprising one or more galectin associated with Mgat5 modified glycan or polylactosamine modified glycan, and isolated lectin-Mgt5 modified glycan lattice comprising an array of multivalent interactions among lectins, Mgat5 modified glycans, polylactosamine modified glycans, and/or glycoproteins. Methods for evaluating a test compound for its ability to regulate receptor clustering through glycans on cell surfaces; and methods for regulating receptor clustering on cell surfaces comprising altering glycans on the cell surface associated with receptor clustering are also discovered.

Abstract: The present invention relates to at least one novel human EPO mimetic hinge core mimetibody or specified portion or variant, including isolated nucleic acids that encode at least one EPO mimetic hinge core mimetibody or specified portion or variant, EPO mimetic hinge core mimetibody or specified portion or variants, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention discloses a system and method using the human ErbB3 receptor, p85-sErbB3, as a negative regulator of heregulin-stimulated ErbB2, ErbB3, and ErbB4 activation. The present invention also discloses a system and method of p85-sErbB3 binding to heregulin with an affinity comparable to that of full-length ErbB3, and competitively inhibiting high affinity heregulin binding to ErbB2/3 heterodimers on the cell surface of breast carcinoma cells. The present invention also uses p85-sErbB3 to inhibit heregulin-induced phosphorylation of ErbB2, ErbB3, and ErbB4 in cells and uses p85-sErbB3 as a negative regulator of heregulin-stimulated signal transduction and as a block for cell growth. The present invention is also directed to nucleic acids and expression vectors encoding p85-sErbB3, host cells harboring such expression vectors, and methods of preparing the protein.

Abstract: The present invention relates to novel mutants of bone morphogenetic proteins (BMPs) useful as inhibitors of heterotopic ossification. Specifically, the present invention related to novel mutants containing only the entire region involved in the formation of finger 2 including the wrist epitope of a BMP with a specific cysteine residue or specific cysteine residues replaced by a different amino acid. The present invention also relates to pharmaceutical compositions containing these mutants and to methods for using the mutants and pharmaceutical compositions in therapy.

Abstract: Adjuvant compositions comprising an effective amount IL-12 and QS-21 are disclosed. Immunogenic, vaccine and pharmaceutical compositions comprising a mixture of antigen and an adjuvant composition comprising an effective amount of IL-12 and QS-21 are also disclosed. These compositions elicit functional cell-mediated and humoral immune responses against at least one antigen. Methods of using the disclosed compositions are also disclosed.

Abstract: The present invention relates to injecting a high specificity cytokine antagonist into a diseased intervertebral disc.

Abstract: A method for constructing stable bioactive fusion proteins of the difficult to express tum or necrosis factor superfamily (TNFSF), and particularly members CD40L (CD 154) and RANKL/TRANCE, with collectins, particularly pulmonary surfactant protein D (SPD) is described. Single trimers of these proteins lack the full stimulatory efficacy of the natural membrane forms of these proteins in many cases. The multimeric nature of these soluble fusion proteins enables them to engage multiple receptors on the responding cells, thereby, mimicking the effects of the membrane forms of these ligands. For CD40L-SPD, the resulting protein stimulates B cells, macrophages, and dendritic cells, indicating its potential usefulness as a vaccine adjuvant. The large size of these fusion proteins makes them less likely to diffuse into the circulation, thereby limiting their potential systemic toxicity.

Abstract: The invention is directed to a fusion protein which includes a first portion including an immunoglobulin (Ig) chain and a second portion including interleukin-7 (IL-7).

Abstract: Human interleukin-18 (IL-18) polypeptides and substitution mutants thereof were conjugated to water-soluble polymers at specific sites on the human IL-18 protein. These conjugated human IL-18 and substitution mutants thereof retain biological activity. These conjugated cytokines demonstrate enhanced and unexpected biological properties when compared to the corresponding unconjugated cytokines.

Abstract: A method for constructing stable bioactive fusion proteins of the difficult to express tumor necrosis factor superfamily (TNFSF), and particularly members CD40L (CD154) and RANKL/TRANCE, with collecting, particularly pulmonary surfactant protein D (SPD) is described. Single trimers of these proteins lack the full stimulatory efficacy of the natural membrane forms of these proteins in many cases. The multimeric nature of these soluble fusion proteins enables them to engage multiple receptors on the responding cells, thereby, mimicking the effects of the membrane forms of these ligands. For CD40L-SPD, the resulting protein stimulates B cells, macrophages, and dendritic cells, indicating its potential usefulness as a vaccine adjuvant. The large size of these fusion proteins makes them less likely to diffuse into the circulation, thereby limiting their potential systemic toxicity.

Abstract: The present invention relates to compositions and methods for diagnosing, monitoring and/or treating an autoimmune or chronic inflammatory disease. In particular, the present invention provides methods for diagnosing, monitoring and treating an autoimmune disease (e.g., rheumatoid arthritis) or chronic inflammatory disease (e.g., systemic lupus erythematosus) based on detecting or altering (e.g., altering expression or methylation status of) autoimmune or chronic inflammatory disease proteins (e.g., CD70 and CD40L). The present invention also provides kits for detecting methylation status of autoimmune or chronic inflammatory disease proteins (e.g., CD70 and CD40L) and for diagnosing, monitoring and/or treating autoimmune or chronic inflammatory diseases.

Abstract: The present invention relates to the use of a cytokine-1, preferably from the IL-1 family more preferably IL-1F7b, or an isoform, mutein, fused protein, functional derivative or fragment thereof, capable of binding to IL-18BP or a mutein, fused protein, functional derivative or fragment thereof and capable of inhibiting a receptor of a cytokine-2, cytokine-2 being a member of the IL-1 family, preferably IL-18, in the manufacture of a medicament for the treatment or prevention of a disease which is caused or aggravated by inducing said receptor of cytokine-2.

Abstract: Methods for treating kinesia (motion sickness) by local administration of a Clostridial toxin, such as a botulinum toxin, to a cranial or neck area of a patient susceptible to motion sickness.

Abstract: The present invention relates to methods of increasing protein expression levels whereby at least one amino acid in a protein amino acid sequence is substituted for the amino acid, proline. Preferably, the substitution occurs within 15 amino acids, more preferably within 10 amino acids and most preferably within 5 amino acids of a cysteine amino acid residue. The present invention not only includes methods for polypeptides with proline substitutions, but also polynucleotides with codon substitutions for which a codon for any amino acid, except proline, is substituted for a codon encoding for proline.