Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: This invention relates to products and methods for treating cancer and for diagnosing tumorigenicity and other diseases associated with alteration in GP88 expression or action. Antagonists to an 88 KDa autocrine growth and tumorigenicity stimulator are provided which inhibit its expression or biological activity. The antagonists include antisense oligonucleotides and antibodies.

Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

Abstract: Disclosed herein are novel methods and compositions for targeting drug delivery systems to specific cells. One aspect relates to a drug delivery system comprising an elastin-like peptide (ELP) component and a ligand selected from the group consisting of mIgA and knob capable of either drug encapsulation or drug attachment. Further aspects relate to drug delivery systems comprising an elastin-like peptide (ELP) component and a ligand; wherein the ligand specifically binds to a receptor selected from the group consisting of CAR and pIgR. Further aspects include the novel transcytosing properties of the elastin-like peptide and the ligand, knob. Also provided are methods and pharmaceutical compositions comprising the disclosed therapeutics.

Abstract: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ?ID?NO:?100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ?ID?NO:?104) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ?ID?NO:?105) c1c2c3Cc5DC7Lc9c10c11c12c13c14Cc16c17c18 (SEQ?ID?NO:?106) d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18 (SEQ?ID?NO:?107) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ?ID?NO:?109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification.

Abstract: The present invention is an antineoplastic agent characterized by including at least one of taxol and taxol derivatives and a protein which is a mutant of diphtheria toxin, having an activity to inhibit a binding between HB-EGF and EGFR and substantially not having a toxicity of diphtheria toxin as active ingredients.

Abstract: In alternative embodiments, the invention provides cell-permeable recombinant or synthetic proteins to modulate autophagy, including a Tat-Atg5K130R (inhibitor of autophagy) and a Tat-Beclin 1 (stimulant or activator of autophagy), and nucleic acids expressing them and methods for making and using them, e.g., to treat conditions and disorders responsive to autophagy modulation (e.g., where autophagy is dysregulated), including neurodegeneration, cystic fibrosis, cancer, heart failure, diabetes, obesity, sarcopenia, aging, ischemia/reperfusion, inflammatory disorders including Crohns, ulcerative colitis, biliary cirrhosis, lysosomal storage diseases, infectious diseases associated with intracellular pathogens including viruses, bacteria, and parasites such as Trypanosomes and malaria.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: Described herein are cell lines and methods for preparing antibodies that bind RANKL, including cell lines that produce blocking antibodies to human RANKL.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: Procedures are described which use solvents to increase the topical insecticidal activity of toxic insect peptides. These procedures comprise drying the peptides, if needed, followed by the addition of either: 1) a polar organic solvent, with or without water, to a dried peptide, or 2) the addition of polar aprotic solvent or other adjuvant to the dried peptide, followed by the addition of either: 1) a polar organic solvent, with or without water, (where a polar aprotic solvent is added first) or 2) a polar aprotic solvent or other adjuvant to the peptide polar organic solvent (where the polar organic solvent is added first), to the peptide formulation.

Abstract: The invention relates to new uses of soluble CEACAM6 or CEACAM8, or substances that are specific to soluble CEACAM8. Another object of the invention concerns the use of CEACAM1-specific and/or CEACAM6-specific compounds for apoptosis prevention in-vitro. The invention also relates to a method for screening compounds, which prevent apoptosis and a method for preventing apoptosis in human granulocytes.

Abstract: The present invention provides methods of reducing or enhancing T cell activation and/or B cell activation in a subject, comprising administering to a subject an effective amount of an inhibitor or enhancer, respectively, of Semaphorin 6D (Sema6D) activity on T cells and/or B cells.

Abstract: Described are soluble gp130 polypeptide monomers and dimers, wherein, in a preferred embodiment, at least one of the three amino acid residues Thr102 Gln113 or Asn114 of the N-terminal Ig-like domain of gp130 is mutated to Tyr102, Phe113 or Leu114, respectively. These mutations, alone or in combination, specifically enhance binding of gp130 to its ligand complex of interleukin-6 and soluble interleukin-6 receptor, thus increasing the biological activity of the gp130 muteins. In a particularly preferred embodiment, all three mutations are combined in the triple mutein Thr102Tyr/Gln113Phe/Asn114Leu (T102Y/Q113F/N114L). Moreover, a pharmaceutical composition containing said monomers or dimers and various medical uses are described.

Abstract: Disorders such as headaches can be treated by administration of a botulinum toxin to a patient suffering therefrom, such as a migraine headache. A combined a fixed site/fixed dose and an optional follow the pain variable dosage and injection site paradigm is disclosed for optimizing clinical effectiveness of botulinum toxin administration for patients suffering headache, particularly chronic migraine.

Abstract: Described herein are compositions and methods for treating Friedreich's Ataxia (FRDA). In some aspects, mutant forms of frataxin which are resistant to ubiquitination are provided. In some aspects, pharmaceutical compositions comprising mutant frataxin are provided. In further aspects, methods of using mutant frataxin are provided.

Abstract: The invention provides a use of a substance that is capable of enhancing the amount and/or activity of DnaJB8, or a functional part, derivative and/or analogue thereof, for counteracting protein aggregation.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: In certain aspects, the present invention provides compositions and methods for treating mucositis.

Abstract: The present invention relates to compositions and methods for treating autoimmune diseases, such as diabetes, by administering to a subject a CTLA4 molecule that block endogenous B7 molecules from binding their ligands.

Abstract: The present invention concerns therapeutic compositions containing proteins that are the variable regions of IgNAR immunoglobulins, denominated vNAR, that specifically bind and neutralizes cytokines involved in a diversity of process such as inflammation and neovascularization, its ability to reach, bind, and neutralize the activity of one antigenic molecule localized in an immunoprivileged organs, are also described.

Abstract: The invention relates to modulating the SIRP?-CD47 interaction in order to increase hematopoietic stem cell engraftment and compounds therefor. In some embodiments, there is provided isolated SIRP? and CD47 polypeptides, fragments and fusion proteins for enhancing hematopoietic stem cell engraftment. Further there is provided methods for increasing hematopoietic stem cell engraftment through administration of the above polypeptides.

Abstract: The marginal zone (MZ) and B1 subsets of B cells, which differ from conventional follicular (FO) B cells both developmentally and functionally, are involved in early responses to infectious pathogens and the production of self-reactive antibodies. A novel gene, mzb1, is expressed at high levels in MZ and B1 B cells but at low level, if at all, in FO B cells. MZB1 is involved in the regulation of proliferation, BCR-mediated signal transduction, and antibody production in B cells. Inhibitors, activators and enhancers of MZB1 expression or activity can be used as immune modulators for research and therapeutic purposes.

Abstract: A method for treating a patient with migraine headache in accordance with the present invention generally includes administering to the patient a therapeutically effective amount of a Botulinum toxin in a pharmaceutically safe form with the administration being on the trigeminal cervical system, for enabling axonal transport of the neurotoxin from distal to central sites. More specifically, the administration includes extramuscular injection of the neurotoxin over the aponeurotic fascia of the scalp for enabling the neurotoxin to diffuse into distal sensory nerves, in order to enable concentration over the occipital-parietal-frontal head region.

Abstract: A number of human beta-glucuronidase variants having higher enzymatic activity at physiological pH as compared with wild-type beta-glucuronidase and uses thereof in prodrug therapy. Also disclosed herein is a method for identifying enzyme variants having elevated enzymatic activity using a mammalian surface display system.

Abstract: Provided herein are compositions and methods for eliciting an immune response against Streptococcus pneumoniae. More particularly, the compositions and methods relate to immunogenic polypeptides, including fragments of PhtD and variants thereof, and nucleic acids, vectors and transfected cells that encode or express the polypeptides. Methods of making and using the immunogenic polypeptides are also described.

Abstract: The present invention relates to the human and murine melanoma inhibitory activity protein-2 (MIA-2) and to the nucleic acids encoding said proteins including a method for producing such proteins by recombinant techniques. The invention also relates to methods for utilizing such proteins for tissue regeneration, tumor treatment including to control the proliferation and differentiation of liver cells in vivo and in vitro. The invention further relates to diagnostic assays including the human and murine antibodies or aptamers and their use in therapy and diagnosis. Further it relates to diagnostic assays applying specific primers for the diagnostic of liver disease.

Abstract: A method of treating a pulmonary disease such as, for instance idiopathic pulmonary fibrosis (IPF), mixed connective tissue disease and asthma, comprising administering an aerosolized interferon such as interferon ? in a therapeutically effective amount is provided herein. Also, pharmaceutical compositions of one or more aerosolized interferon(s) alone or in combination with other therapeutic agents are provided.

Abstract: Disclosed herein are multi-component formulations for enzymatically producing aqueous solutions of peroxycarboxylic acids suitable for use in, e.g., disinfectant and/or bleaching applications. The multi-component peroxycarboxylic acid formulations comprise at least one carbohydrate esterase family 7 enzyme having perhydrolytic activity.

Abstract: Methods and compositions for diagnosing and treating diseases, particularly cancer, associated with differential expression of cancer-associated targets (CAT) in disease cells compared to healthy cells are provided. Also provided are antagonists and agonists of CAT, and methods for screening agents that modulate CAT level or activity in vivo or in vitro.

Abstract: The present invention is directed to fusion polypeptides comprising Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.

Abstract: Provided herein are methods of enhancing in vivo efficacy of an active agent, comprising: administering to a subject an active agent that is coupled to a bioelastic polymer or elastin-like peptide, wherein the in vivo efficacy of the active agent is enhanced as compared to the same active agent when administered to the subject not coupled to (or not associated with) a bioelastic polymer or ELP.

Abstract: A composition for delivering cargo molecules across biological membranes is provided comprising (i) a peptide comprising consecutive amino acid residues having the sequence set forth in SEQ ID NO 1 for the transport of a cargo molecule across a biological membrane and (ii) the cargo molecule, wherein the cargo molecule is not a peptide comprising amino acid residues having the sequence set forth in SEQ ID NO 4. Methods of delivering cargo molecules across biological membranes are also provided. Methods of treating a tumor, cancer, a metabolic disorder, and a cardiovascular disorder are also provided.

Abstract: An isolated protein is provided for use in treatment of a condition selected from the group consisting of Alzheimer's disease, familial Danish dementia and familial British dementia in a mammal, including man. The isolated protein is selected from the group consisting of proteins comprising an amino acid sequence having at least 70% identity to residues 90-236 of Bri2 from human; and proteins comprising an amino acid sequence having at least 70% identity to any one of the Brichos domains of Bri2 from human, chimpanzee, bovine, pig, mouse and rat.

Abstract: Aspects of the invention provide methods for treatment of nonalcoholic steatohepatitis and associated liver fibrosis. In particular, aspects of the invention relate to the use of a therapeutic formulation comprising a galacto-rhamnogalacturonate compound for the treatment of nonalcoholic steatohepatitis and associated liver fibrosis.

Abstract: The present invention relates generally to stable formulations comprising CTLA4Ig molecules, including lyophilized, and liquid formulations for administration via various routes including, for example, routes such as intravenous (IV) and subcutaneous (SC) for treating immune system diseases and tolerance induction.

Abstract: The present invention relates to pharmaceutical compositions for a combination therapy with a cytokine antagonist and a corticosteroid. By means of the combination therapy diseases such as osteoarthritis, tendon injuries and/or degenerative spinal diseases can be treated.

Abstract: A novel mammalian catecholamine-regulated protein called CRP40 is identified. This protein, and nucleic acid encoding same, is useful in methods of diagnosing and treating hypodopaminergic neurological disease, such as Parkinson's disease, multisystem atrophy, lewy body dementia, schizophrenia, and bipolar disease.

Abstract: Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Abstract: The invention relates to conjugates that bind to Her2/neu, methods of using conjugates that bind to Her2/neu and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express Her2/neu.

Abstract: The present application relates to methods of producing exosomes. The application also provides a method for preparing a protein composition comprising culturing an exosome-producing cell expressing a Nef-fusion protein comprising a Nef-derived peptide fused to a protein of interest; isolating exosomes from the exosome-producing cell culture; and purifying the protein of interest from the isolated exosomes. The application further discloses compositions that comprise exosomes containing the Nef-fusion protein, as well as methods of using the Nef-fusion protein and exosomes containing the Nef-fusion protein.

Abstract: The invention in suitable embodiments is directed to an isolated protein comprising one or more amino acid sequences, each amino acid sequence capable of being functionalized and/or attached in whole and/or in part to one or more or a plurality of elements of one or more types including to cargo elements, forming a composition of elements suitable for use as an in vivo and/or in vitro medicament to treat one or more biological species.

Abstract: Therapeutic and cosmetic uses and applications of calreticulin are provided. In particular, the invention relates to therapeutic and cosmetic uses and applications of calreticulin to a patient in need of such treatment including in tissue repair, wound healing, ulcers, reducing scar formation, and reducing or eliminating wrinkles.

Abstract: The present invention relates generally to methods for preventing and/or treating pancreatic disorders, particularly those related to diabetes, by administering a neurturin protein product.

Abstract: This invention relates to compositions and methods comprising “lymphotoxin-?-receptor blocking agents”, which block lymphotoxin-? receptor signalling. Lymphotoxin-? receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-? receptor extracellular domain that act as lymphotoxin-? receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-? receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-? receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-? receptor signalling is provided.

Abstract: The present invention provides splice variants of myostatin that promote muscle growth, and include polynucleotides and polypeptide sequences, constructs comprising the sequences and compositions for regulating muscle growth and treating diseases associated with muscle tissue. The splice variants include the consensus sequence X1 I F L E X2 X3 X4 Q X5 C S I L X6 X7 X8 X9 X10 wherein X1 is I or L, X2 is V or L, X3 is Y, C, G or S, X4 is I or F, X5 is F or L, X6 is G or E, X7 is E or V, X8 is A or T, X9 is A or V and X10 is absent, F or L. The present invention also provides for the use of the present sequences in identifying animals with altered muscle mass, and for use in selective breeding programs to produce animals with altered muscle mass.

Abstract: An isolated oxidation-resistant ApoA1 variant dimer includes a first oxidation-resistant ApoA1 variant polypeptide monomer and a second oxidation-resistant ApoA1 variant polypeptide monomer, wherein at least one of the first and the second monomers comprises at least one amino acid substitution of a tryptophan residue for an oxidation resistant amino acid, or a functional fragment or variant thereof. Methods for treating a disease or disorder comprises administering to a subject in need thereof, a therapeutically effective amount of an isolated oxidation-resistant ApoA1 variant dimer, an oxidation-resistant ApoA1 variant monomer, an oxidation-resistant ApoA1 monomer-lipid complex, a lipid complexed oxidation-resistant ApoA1 variant monomer, a lipid complexed oxidation-resistant ApoA1 variant dimer, or combinations thereof to the subject to enhance cholesterol efflux activity in the presence of an oxidant.

Abstract: Recombinant proteins comprised of multiple selectin binding domains derived from the glycopeptide PSGL-1, in a novel tandem configuration, are disclosed, including their fusions with immunoglobulins and/or other polypeptides. Polynucleotides encoding such proteins, compositions and kits containing such proteins, and methods of using such proteins are also disclosed.

Abstract: The invention describes isolated mTOR-associated proteins (“mTOR-APs”) as well as isolated variants and fragments thereof and the isolated nucleic acids encoding them. The invention also describes vectors and host cells containing nucleic acid encoding an mTOR-AP polypeptide and methods for producing an mTOR-AP polypeptide. Also described are methods for screening for compounds which modulate mTOR-AP activity and methods for treating or preventing a disorder that is responsive to mTOR-AP modulation.