Abstract: The present invention relates to novel Death Domain Containing Receptor (DR3 and DR3-V1) proteins that are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR3 and DR3-V1 proteins. DR3 and DR3-V1 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are antibodies and fragments thereof that bind to polypeptides of the invention. The invention further relates to screening methods for identifying agonists and antagonists of DR3 and DR3-V1 activity.

Abstract: This invention is directed to the targeting of proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule and methods of use thereof. Nucleic acids, vectors comprising the same, and compositions for targeting proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule are disclosed as are methods of use thereof for stimulating or enhancing immune responses in a subject.

Abstract: The present invention relates to methods for the treatment and repair of cartilage, including cartilage damaged by injury or cartilaginous disorders, including arthritis, comprising the administration of insulin and/or insulin variants. Optionally, the administration may be in combination with a cartilage agent (e.g., peptide growth factor, catabolism antagonist, osteo-, synovial, anti-inflammatory factor), in an extended- or sustained-release form. Alternatively, the method provides for the treatment and repair of cartilage damaged by injury or cartilaginous disorders comprising the administration of insulin and/or insulin in combination with standard surgical techniques. Alternatively, the method provides for the treatment and repair of cartilage damaged by injury or cartilaginous disorders comprising the administration of chondrocytes previously treated with an effective amount of insulin and/or insulin variant.

Abstract: Proteins that bind IL-17 and/or IL-17F are described along with there use in composition and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

Abstract: The present invention relates to human interferon gamma variants with improved thermostability, to a nucleic acid encoding said variants, to a pharmaceutical composition containing them, and to their use for the treatment of a viral infection and of cancer.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: The present invention relates to biologically active polypeptides linked to one or more accessory polypeptides. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: Multi-dose active agent packages and methods for using the same for treating a subject for a condition are provided. Aspects of the invention include a multi-dose active agent package containing a plurality of unit dosage forms of an active agent configured to modulate at least a portion of a subject's autonomic nervous system during at least one season of the year. The active agent is present in an amount sufficient to alter the parasympathetic activity/sympathetic activity ratio of the subject in a manner effective to treat the subject for the condition. The subject active agent packages and methods find use in the treatment of a variety of different conditions, including disease conditions that increase in severity and/or occurrence during one or more seasons of the year. Also provided are kits for use in practicing the subject methods.

Abstract: The present invention relates to novel compositions having anti-viral activity and in particular it relates to synergistic compositions active against Hepatitis C virus (HCV). The invention also relates to methods for retarding, reducing or otherwise inhibiting HCV growth and/or functional activity.

Abstract: Compositions and methods for manufacturing polymers are disclosed. Compositions include novel plastics, including films and shaped forms comprising polymer matrices that are biologically compatible and biodegradable. Such plastics may comprise polymers derived from natural sources. Further, such plastics are useful in biological systems for wound repair, implants, stents, drug encapsulation and delivery, and other applications. The disclosed methods comprise mild manufacturing processes such that various additives, such as biologically active proteins, sugars, lipids, and the like may be incorporated into the polymer matrix without subsequent loss of bioactivity during processing. Additionally, methods of manufacture for controlling mechanical properties, such as elasticity, pliancy, and the porosity of such plastics are disclosed.

Abstract: The invention relates to interferon-? molecules having certain O-linked oligosaccharide structures.

Abstract: A method of treating cancer in a subject in need thereof comprises administering said subject reserpine, yohimbine, an analog thereof, or a pharmaceutically acceptable salt or prodrug thereof, in an amount effective to treat the cancer. Compounds and compositions useful for carrying out the method are also described.

Abstract: Provided herein are phosphothiophene and phosphothiazole compounds, for example, of any of Formulae I, IA, IIA, IIIA, IVA, VA, VIA, VIIA, IB, IIB, IIIB, IVB, VB, VIIB and VIIB disclosed herein, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host infected with HCV.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Pyrazolo[1,5-a]pyridines are described, including methods for their preparation, and their use as agents or drugs for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Embodiments disclosed in the present application relate to a composition that can include a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof. Additional embodiments disclosed relate to methods for treating a disease condition such as a hepatitis C virus infection, liver fibrosis and/or impaired liver function with a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two therapeutic agents and one PEG moiety. In alternative embodiments, the therapeutic agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-?2b. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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 invention relates to a compound of general formula (I-0): wherein R1 means a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C3-C6 cycloalkyl group; R2, R3, R4 and R5 mean a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, or a halo-C1-C6 alkoxy group; R6 means a hydrogen atom, or a C1-C6 alkyl group; R7a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, a hydroxy-C1-C6 alkyl group, -Q2-N(R1c)R1d or a nitrogen-containing heterocyclic group; R8a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group or a hydroxy-C1-C6 alkyl group; or R7a and R8a form, as taken together, a C2-C6 alkylene group, or R7a and R8a and the ring atoms to which they bond may form a spiro ring or a bicyclo ring; and X and Y mean a methine group or a nitrogen atom.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention provides a composition comprising naked humanized, chimeric, and human anti-CEA antibodies and a therapeutic agent, which is useful for treatment of CEA expressing cancers and other diseases, and methods of use in treatment using this composition.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The invention provides for a formulation for coating one or more microprojections which reduces or minimizes the loss of counterions from the coating in order to achieve a pH-stabilized formulation.

Abstract: The present invention encompasses IL-1? binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1? and neutralize IL-1? activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting IL-1? and for inhibiting IL-1? activity, e.g., in a human subject suffering from a disorder in which IL-1? activity is detrimental.

Abstract: The invention provides a peptide comprising an agonist of a MHC Class I binding native sequence having amino acid substitution(s) and enhanced immunogenicity compared to the native sequence. The invention also provides methods comprising the administration of the peptide.

Abstract: The embodiments provide compounds of the general Formula II, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments also provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract: The present disclosure demonstrates for the first time that Th-17 cells are the product of a distinct CD4+ T cell lineage with unique developmental and functional characteristics. The developmental signals required for Th-17 commitment and development are also described. As a result, the teachings of the present disclosure provide a basis for understanding the developmental pathway of Th-17 cells and offer novel avenues to modulate (stimulate or inhibit) this developmental program and offer new methods for the treatment and prevention of disease states and conditions related to aberrant activity of Th-17 cells.

Abstract: Compositions comprising CD80-targeted therapeutics and methods of using these compositions are provided for the treatment of a disease or disorder in which CD80-expressing cells or regulatory T cell function contribute to or exacerbate the associated pathology.

Abstract: The present invention comprises a composition with means to inhibit the function of the inflammatory cytokine IL-1 and methods for using this composition to treat inflammatory disease of ocular and adnexal tissues by topical administration. The present invention also discloses devices for delivering this composition to target tissues.

Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

Abstract: Humanized antibodies are provided that specifically bind HLA-DR. The antibodies recognize the epitope recognized by the murine monoclonal antibody L243. Processes for preparing such antibodies, pharmaceutical compositions containing such antibodies, and clinical therapeutic and diagnostic, as well as research-related uses for such antibodies, are provided.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: The present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

Abstract: A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, Z, Y, X, M, W, n and m are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes 5 for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: The present invention relates to a composition, method and kit for treating cancer. The treatment comprises administering a pre-sensitizing agent to a tumor or subject, and administering a cancer therapy to the tumor cells or subject. The pre-sensitizing agent increases or induces the apoptosis of the tumor cells, as compared to the rate of apoptosis of tumor cells that have not been pre-sensitized prior to receiving the cancer therapy. In another aspect, the invention relates to a kit comprising a pre-sensitizing agent and a cancer therapy.

Abstract: Recombinant immunogenic compositions, and methods for the manufacture and use, are provided for the prevention and treatment of intracellular pathogen diseases in humans and animals. The recombinant immunogenic compositions express high levels of recombinant proteins in vectors that do not harbor an antibiotic resistance marker (“unmarked”).

Abstract: The present invention provides methods and compositions designed for treating a subject suffering from skin conditions, disorders or diseases. The compositions include fetal skin cell proteins obtained from fetal skin cells after induced cell lysis.

Abstract: The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients.

Abstract: The invention relates to an inhibitor of endogenous human interferon-gamma (hIFN-ϝ) in autoimmune diseases, especially in multiple sclerosis. More precisely, the invention relates to inactivated protein derivatives of the hIFN-ϝ with preserved affinity to the hIFN-ϝ receptor. The derivatives represent genetically modified variants of hIFN-ϝ, where the C-terminal part of the molecule is either deleted or replaced with a polypeptide sequence of another human protein and a recombinant hIFN-ϝ, inactivated by physical or chemical methods.

Abstract: The present invention is directed to therapeutic methods using antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat cachexia, fever, weakness and/or fatigue in a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

Abstract: The present invention provides methods for treating a flavivirus infection, including hepatitis C virus (HCV) infection, in an individual suffering from a flavivirus infection. In some embodiments, the methods involve administering to an individual in need thereof an effective amount of an agent that inhibits enzymatic activity of a membrane-bound ?-glucosidase inhibitor. In other embodiments, the methods involve administering to an individual in need thereof effective amounts of an ?-glucosidase inhibitor and at least one additional therapeutic agent.

Abstract: The compound 4-{4-[({3-tert-Butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-carbamoyl)amino]-3-chlorohenoxy}-N-methylpyridine-2-carboxamide and alternatives forms thereof (e.g., salts, hydrates, solvates, prodrugs, polymorphs and metabolites); pharmaceutical compositions which contain them and methods for treating cancer using them.

Abstract: Oral insulin formulations and processes for preparing oral insulin formulations are provided.

Abstract: Soluble PH20 polypeptides are provided, including extended soluble PH20 polypeptides, and uses thereof. Also provided are other C-terminally truncated PH20 polypeptides and partially deglycosylated PH20 polypeptides and uses thereof.

Abstract: The present invention is intended to provide a diagnostic method for paratuberculosis by which an animal infected with Mycobacterium avium subsp. Paratuberculosis can be diagnosed at a high sensitivity in the sub-clinical infection stage before the specific antibody level begins to increase and a large number of specimens can be treated. The present invention provides: a diagnostic method for paratuberculosis characterized by collecting the blood of a subject animal, adding an anti-IL-10 antibody and a Mycobacterium avium subsp.