Abstract: The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.

Abstract: A novel approach to discover new drugs against MS and other autoimmune diseases is disclosed. The p40 family of cytokines has four members which include interleukin-12 (IL-12), the p40 monomer (p40), the p40 homodimer (p402), and the IL-23. To facilitate the studies on p402 and p40, neutralizing monoclonal antibodies (mAb) against mouse p402 and p40 were generated for the first time. MS and other autoimmune disease drug therapies including recombinant p40 and/or monoclonal antibody against p402 (mAb-p402 a3-1d) are disclosed.

Abstract: The invention is concerned with a fusion protein comprising interleukin 10 and interleukin 4, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.

Abstract: The present invention relates to polypeptides which share primary sequence with human IL-2, except for several amino acids that have been mutated. The mutations introduced substantially reduce the ability of these polypeptides to stimulate in vitro and in vivo regulatory T cells (T CD4+CD25+FoxP3+) and make them more effective in the therapy of murine transplantable tumors. Also includes therapeutic uses of these mutated variants, used alone or in combination with vaccines for the therapy of diseases such as cancer or infections where the activity of regulatory T cells (Tregs) is relevant. In another aspect the present invention relates to pharmaceutical compositions comprising as active principle the polypeptides disclosed. Finally, the present invention relates to the therapeutic use of the polypeptidess and pharmaceutical compositions disclosed due to their modulating effect of the immune system on diseases like cancer and chronic infectious diseases.

Abstract: The invention relates to IL-22 polypeptides, IL-22 Fc fusion proteins and IL-22 agonists, composition comprising the same, methods of making and methods of using the composition for the treatment of diseases. The invention also relates to IL-22 receptor associated reagents and methods of use thereof.

Abstract: Provided are methods of treatment for tumors. In particular, methods are provided for use of a chemically modified IL-10 to treat tumors.

Abstract: The present invention relates to the use of inclusion bodies as vehicles for therapeutic protein delivery. This method is applicable to the delivery of therapeutic proteins to intracellular locations. In addition, the invention also relates to the administration of a cell or a pharmaceutical composition comprising inclusion bodies formed by therapeutic proteins. These inclusion bodies formed by therapeutic proteins could be used for the treatment of different diseases.

Abstract: The present invention relates to chimeric (preferably, bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds preferably covalently bind to the urokinase receptor and recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and/or antibody-dependent cellular cytotoxicity (ADCC) against a large number and variety of cancers, thus providing cancer cell death and/or an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.

Abstract: Described are biomarkers including TOX useful for the diagnosis or prognosis of T cell malignancy. A level of a biomarker is determined in a sample from a subject and compared to a control level, wherein an increased level of the biomarker in the sample relative to the control level indicates that the subject has T cell malignancy. The T cell malignancy may be a cutaneous T cell lymphoma (CTCL) such as mycosis fungoides or Sezary syndrome.

Abstract: The invention is directed to ?1-6 glucans, compositions, diagnostic kits, and devices comprising the same, and methods of use thereof in modulating immune response and treating, delaying progression of, reducing the incidence or severity of cancer, infection, inflammation, and autoimmune diseases. The ?1-6 glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety. The ?1-6 glucans of certain embodiments of the invention recruit immunoglobulin G antibodies to mediate complement and neutrophil killing. The conjugated ?1-6 glucans of certain embodiments of the invention are targeted to cells to stimulate the immune response at the target location by activating complement-mediated lysis and recruitment of neutrophils.

Abstract: (Problems) To provide a therapeutic agent for infections comprising granulysin as an active ingredient which has little side effect and no cytotoxicity and to which bacteria can hardly acquire resistance, and a treatment method using the same. (Means for Solving Problems) The present invention provides a therapeutic agent for infections comprising as active ingredient: 15K granulysin, a combination of 15K granulysin and 15K granulysin in vivo expression vector, a combination of 15K granulysin and at least one interleukin selected from IL-6, IL-23 or IL-27, a combination of 15K granulysin in vivo expression vector and at least one interleukin selected from IL-6, IL-23 or IL-27, or a combination of 15K granulysin in vivo expression vector and HSP65DNA and IL-12DNA in vivo expression vector, which enhances killing effects on bacteria and has less side effect, and to which bacteria can hardly acquire resistance, and a treatment method using the same.

Abstract: Featured herein are vehicle formulations and formulations containing a chimeric cytokine designed for e.g., ocular delivery.

Abstract: The present invention provides methods for purifying a polypeptide from a composition comprising the polypeptide and at least one contaminant by overloading a chromatography material and eluting the product.

Abstract: Influenza virus infection and the resulting complications are a significant global public health problem and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain.

Abstract: The invention relates to a pharmaceutical formulation for sustained delivery of a therapeutic agent, preferably a protein, polypeptide, an antibody or an antibody fragment, comprising one or more gel forming peptides wherein the formulation exhibits sustained delivery for at least two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, eight weeks, nine weeks, ten weeks, eleven weeks, twelve weeks or more. In one embodiment, the invention relates to a formulation comprising self-assembling peptides that undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. The formulation can provide sustained release of antibody and antibody fragments, in particular, IgG. Antibody diffusivities can be decreased with increasing hydrogel nanofiber density, providing a means to control the release kinetics.

Abstract: The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.

Abstract: Human lubricating gels, methods and kits for delivering a therapeutic agent to a target tissue site beneath the skin of a patient utilizing human lubricating gel are provided, the human lubricating gel being capable of adhering to the target tissue site and comprising one or more biodegradable formulations containing an effective amount of the therapeutic agent. In various embodiments, the human lubricating gel is sprayable and hardens after contacting the target tissue site.

Abstract: The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

Abstract: Methods of treating blood disorders are described.

Abstract: Embodiments are directed to compositions and methods of treating migraine and related neurological disorders. In certain aspects, methods and compositions are for reducing cortical spreading depression and/or suppressing the neurochemical basis for chronic and acute migraine events, and provide methods and pharmaceutical compositions related to both acute and preventive therapies for migraine events and related headaches.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: This invention relates to antibodies and antigen binding fragments and conjugates containing same, and/or alternative scaffolds, specific for LSR molecules, which are suitable drugs for immunotherapy and treatment of specific cancer.

Abstract: The present invention relates to methods and compositions for modulating T cells. The modulation includes suppressing or inducing regulatory T cells or cytotoxic T cells.

Abstract: Methods for diagnosing and treating Alzheimer's disease are provided. In particular, methods of restoring blood-brain barrier integrity and/or promoting vascular reversion in a person suffering from Alzheimer's disease by administering an anti-angiogenic agent or an agent that is capable of restoring tight junction integrity. Methods of preventing or delaying the onset of Alzheimer's disease in a subject are also provided.

Abstract: The present invention relates to a combination of an anti-EDb fibronectin antibody-IL-2 fusion protein, and a molecule binding to B cells, B cell progenitors and/or their cancerous counterpart and uses thereof.

Abstract: The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

Abstract: Provided are recombinant antibodies comprising one or more peptides fused to the C-terminus of the light chain constant region. Recombinant immunocytokines comprising a cytokine fused to the C-terminus of the light chain constant region are described and shown to be surprisingly active.

Abstract: The invention relates to a novel cell derived from the human body, where said cell comprises a Clever-1 receptor; to a method for affecting the immune system of an individual and for treatment of diseases or conditions related to the function of the immune system and to methods for screening of cancer patients that may respond to an anti-Clever-1 therapy or for diagnosing of a pregnancy complication or for estimating the risk of such complication in a pregnant woman.

Abstract: This disclosure relates to compounds, compositions and methods of epigenetically transforming cells. In certain embodiments, the disclosure relates to methods of generating epigenetically altered cells comprising mixing isolated cells with compositions disclosed herein under conditions such that epigenetically altered cells are formed. In certain embodiments, the disclosure contemplates inducing cells, such as adult somatic cells or cells that are not naturally pluripotent, into cells with chemically induce pluripotency. In certain embodiments, the disclosure contemplates certain compounds disclosed herein, compounds disclosed herein optionally substituted with one or more substituents, derivatives, or salts thereof, for these purposes.

Abstract: An improved thrombopoietin mimetic, the bis-(monoethanolamine) salt of 3?-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2?-hydroxy-[1,1?-biphenyl]-3-carboxylic acid.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

Abstract: Embodiments of the invention are directed to methods of diagnosing eosinophilic gastritis (EG), or remission therefrom in a subject, wherein the methods include applying a sample from the subject to a diagnostic panel that contains selected markers for EG, analyzing the results thereof, and making a determination as to the EG status of the subject. Embodiments of the invention are also directed to methods of monitoring the pathological development or medical prognosis of EG in a subject. Embodiments of the invention are also directed to use of CDH26 as a marker for EG, eosinophilic esophagitis, or allergic inflammatory conditions. Embodiments of the invention also relate to the use of anti-CDH26-based therapeutics to treat allergic inflammatory conditions.

Abstract: Compositions comprising TL1A-Ig fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin).

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Abstract: The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Abstract: This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.

Abstract: The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.

Abstract: The present invention provides methods of forming a solid, biodegradable implant in-situ in a body by administering a liquid pharmaceutical composition comprising an effective amount of a biocompatible, water-insoluble, biodegradable polymer and an effective amount of a therapeutic peptide covalently modified with one or more lipophilic or amphiphilic moieties, which are dissolved or dispersed in a biocompatible, water-soluble organic solvent. This invention also provides related compositions and methods.

Abstract: This disclosure relates, at least in part, to a method of treatment. In one embodiment, the method of treatment comprises administering to a subject in need of such treatment a first therapeutic agent including compound (1): or a pharmaceutically acceptable salt thereof in combination with a second therapeutic agent, wherein the first therapeutic agent and the second therapeutic agent are administered either simultaneously or sequentially.

Abstract: The invention relates to a novel use of the members of the IL-10 cytokine family in wound healing. Particularly, the invention relates to the use of the member of the IL-10 cytokine family in the promotion of the proliferation and the migration of keratinocyte cells in wound healing.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for HGF. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-HGF antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-HGF antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-HGF antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with HGF.

Abstract: The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

Abstract: ?-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of ?-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising ?-mannosylceramide, as well as methods of treatment of tumors are also provided.

Abstract: The object of the invention is a DNA vaccine, method of inducing the immune response, antibodies specifically recognising the haemagglutinin H5 of an influenza virus and application of the DNA vaccine. According to the invention, one or two-fold immunisation of hens with DNA vaccine containing a cDNA encoding the modified H5 haemagglutinin HA protein, i.e. with the deletion of the cleavage site between HA subunits (this provides for greater safety of the vaccines). Moreover, the encoding region of the HA is modified in such a way that protein production in the bird cells should achieve maximal yield. The main modification is codon optimisation for the hens and deletion of the site of proteolytic cleavage between subunits HA1 and HA2.

Abstract: Therapies effective for the treatment and prevention of cancer and other diseases are disclosed. These methods include the administration of therapeutically effective amounts of agents that increase the local production of effector cell-attracting chemokines within tumor lesions, with concomitant suppression of local production of undesirable chemokines that attract regulatory T(reg) cells. These methods include administering to the subject therapeutically effective amounts of a Toll-like receptor (TLR) agonist or other activator of NF-KB pathway in combination with a blocker of prostaglandin synthesis or a blocker of prostaglandin signaling, in combination with a type-1 interferon, or in combination with both a blocker of prostaglandin synthesis or signaling and with a type-1 interferon.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Abstract: The invention relates to a stable amorphous form of (5-Fluoro-2-methyl-3-quinolin-2-ylmethyl-indol-1-yl)-acetic acid and its use in the treatment of conditions mediated by the action of PGD2 at the CRTH2 receptor.

Abstract: Disclosed is a compound of formula (I), wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the present application.

Abstract: The present invention relates to a method of transplanting haematopoietic precursor cells into a subject in need thereof which involves culturing the haematopoietic precursor cells in the presence of a population of cells enriched for STRO-1bright cells. The method of the present invention is useful in the treatment of haematological disorders.