Abstract: The present invention concerns combinations of two or more agents for inducing an immune response to cancer or infectious disease. Agents may include leukocyte redirecting complexes, antibody-drug conjugates, interferons (preferably interferon-?), and/or checkpoint inhibitor antibodies. The leukocyte redirecting complexes have at least one binding site for a leukocyte antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other leukocyte antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of cells associated with cancer or infectious disease.

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2?-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

Abstract: In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (H2O2), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of H2O2 and concentration of HRP in the solution when the molarity of H2O2 is limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of H2O2 may be selected to affect the differentiation or growth rate of the cells in the hydrogel. Also, the hydrogel system may be used for sustained delivery of a therapeutic protein, for example in the treatment of liver cancer, fibrosis or hepatitis.

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: Methods are provided for treating a subject for at least one condition that includes inflammation, a blood clotting condition and autonomic nervous system dysfunction such as adrenergia, e.g., simultaneously. Also provided are kits for use in practicing the subject methods.

Abstract: New pyrazole derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, provided herein are compounds according to Formula 1001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein Base, Y, Z, A, RC and RD are as described herein.

Abstract: This application covers a novel PEGylated interferon and a novel crystalline form of interferon which are useful, inter alia, for detailed structural analysis of interferon as well as treatment and prevention of viral infections and hyperproliferative diseases such as leukemia.

Abstract: Provided herein are tetrazolone FASN inhibitors of the formula (I): or a pharmaceutically acceptable form thereof; wherein the variables RA, RB and RC are defined herein. Also provided herein are pharmaceutical compositions of the compounds provided herein as well as methods of their use for the treatment of various disorders such as hyperproliferative disorders, inflammatory disorders, obesity-related disorders and microbial infections.

Abstract: Novel chimeric moieties that show significant efficacy against cancers are provided. In certain embodiments the chimeric moieties comprise a targeting moiety attached to an interferon. In certain embodiments, the chimeric moieties comprise fusion proteins where an antibody that specifically binds to a cancer marker is fused to interferon alpha (IFN-?) or interferon beta (IFN-?).

Abstract: The present invention embraces Niemann-Pick C1-like 1 protein antagonists and agents that inhibit hepatic virus infection for use in the prevention and treatment of a hepatic virus infection.

Abstract: The present invention relates:—to 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo-[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide dihydrochloride salt of formula (II): or a tautomer, solvate or hydrate thereof;—to methods of preparing said dihydrochloride salt;—to said dihydrochloride salt for the treatment and/or prophylaxis of a disease;—to the use of said dihydrochloride salt for the preparation of a medicament for the treatment and/or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, more particularly for the treatment or prophylaxis of a cancer, particularly lung cancer, in particular non-small cell lung carcinoma, colorectal cancer, melanoma, pancreatic cancer, hepatocyte carcinoma, pancreatic cancer, hepatocyte carcinoma or breast cancer;—to a pharmaceutical composition comprising said dihydrochloride salt; and to a pharmaceutical combination comprising said dihydrochloride salt in combination with one or more further pharmaceutical agent

Abstract: The present invention provides combinations of (a) an immunoconjugate comprising at least one antigen-binding moiety and an effector moiety, and (b) an antibody engineered to have increased effector function, for use in treating a disease in an individual in need thereof. Further provided are pharmaceutical compositions comprising the combinations, and methods of using them.

Abstract: A compound is selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier of excipient. A method of treating a HCV infection in a subject comprises administering to the subject a therapeutically effective amount of selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof. A method of inhibiting or reducing the activity of HCV polymerase in a subject or in a biological in vitro sample comprises administering to the subject or to the sample a therapeutically effective amount of selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed are therapeutic methods for ex-vivo activation of immune cells from a cancer patient for the purpose of inducing tumor regression and/or suppressing metastasis and/or tumor recurrence. In one embodiment mononuclear cells of a patient are isolated from peripheral blood and activated by a combination of innate immune system activators together with means allowing for T cell activation.

Abstract: It is disclosed a method for the treatment of HBV infection or HBV/HDV co-infection, the method comprising administering to a subject in need of treatment a first pharmaceutically acceptable agent that removes the hepatitis B surface antigen from the blood and a second pharmaceutically acceptable agent which stimulates immune function.

Abstract: The present invention relates to antiviral therapies and compositions for treating or preventing Hepatitis C infections in patients and relates to other methods disclosed herein. The invention also relates to kits and pharmaceutical packs comprising compositions and dosage forms. The invention also relates to processes for preparing these compositions, dosages, kits, and packs.

Abstract: The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V-domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig). The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions.

Abstract: This invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof wherein C* represents a diastereomeric carbon comprising a mixture of R and S isomers wherein the R isomer is greater than 50% of the mixture.

Abstract: The present invention provides substituted azaindole prodrugs, methods of making said prodrugs, pharmaceutical compositions of said prodrugs and methods of using said prodrugs and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as cancer.

Abstract: The present invention concerns compositions and methods of use of T-cell redirecting complexes, with at least one binding site for a T-cell antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other T-cell antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells to induce T-cell-mediated cytotoxicity of cells associated with a disease, such as cancer, autoimmune disease or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon-based agents that comprise interferon-?, interferon-?, interferon-?1, interferon-?2 or interferon-?3.

Abstract: Increased in vivo and/or in vitro stability is imparted to a biologically active protein by fusing to an amino acid sequence consisting of at least about 100 amino acid residues, which consist essentially of Alanine, Serine and Proline, which form a random coil conformation. Specific examples are described. Also described are related nucleic acids, vectors and cells encoding such amino acids; compositions of biologically active proteins fused to a random coil domain, and methods of making and using the compounds and compositions of the invention.

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: Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful therapeutic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection, diagnosis and/or treatment of cancer, such as pancreatic cancer. The antibodies, such as PAM4 antibodies, bind to a PAM4 antigen that shows unique cell and tissue distributions compared with other known antibodies such as CA19.9, DUPAN2, SPAN1, Nd2, B72.3, and Lea and Le(y) antibodies that bind to the Lewis antigens.

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: Methods and compositions for contributing to the treatment of cancers, especially ovarian tumors, are disclosed. The methods and compositions utilize an endothelin B agonist (ETB) to enhance the delivery and resulting efficacy of chemotherapeutic agent(s) (e.g., cisplatin and/or cyclophosphamide).

Abstract: The present disclosure provides a method of increasing an immune response in an individual, the method involving administering to an individual in need thereof an inhibitor of SIRT1. The present disclosure provides a method of reducing an immune response, e.g., to treat chronic immune hyperactivity, the method generally involving administering to an individual in need thereof an activator of SIRT1. The present disclosure provides a method of modulating activation and differentiation of CD4+ T cells.

Abstract: Therapeutic methods are disclosed herein.

Abstract: The present invention relates to substituted fused tricyclic compounds of formula (I) or (Ia), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, co-crystals, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by JAK activity. The compounds of the present invention are useful in the treatment, prevention or suppression of diseases and disorders mediated by JAK activity.

Abstract: An immunogenic product including IFN? coupled to a carrier protein molecule is capable to induce in vivo anti-IFN? antibodies and is useful in treating IFN? related conditions.

Abstract: Methods for preparing polymer-drug conjugates are provided. The disclosed methods involve polymeric reagents comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. Related methods, compositions, preparations, and so forth are also provided.

Abstract: Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of cytopathic diseases. Cytopathic diseases may be caused by a variety means such as viral infections like HIV and AIDS, or the development of neoplasms in a mammalian subject. The methods and compositions of the invention are effective for inhibiting de novo HIV infection, upregulating viral expression from latent provirus, inhibiting HIV-induced cytopathic effects, down regulating the HIV receptor, increasing Th1 cytokine expression, decreasing Th2 cytokine expression, increasing ERK phosphorylation, inducing apoptosis in malignant cells, inducing remission, maintaining remission, as chemotherapeutic agents, as well as for decreasing symptoms of cytopathic diseases and opportunistic infections that may accompany such diseases.

Abstract: The present application provides for a compound of Formula IV, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

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: The present invention relates to host immune factors and antibiotics and, more particularly, to a system and method for controlling and reducing the antibiotic tolerance of bacterial persister cells with host immune factors.

Abstract: The invention relates to a method for the immune activation of NK cells by the reduction or inhibition of the Cbl-b function in said cells. This stimulates the congenital immune system and thus permits the therapy of appropriate diseases.

Abstract: The present invention relates to peptidomimetic compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

Abstract: Disclosed is an interferon-? (IFN-?) fused protein having IFN-? fused to a cytoplasmic transduction peptide (CTP). The disclosure relates to a fused protein wherein a CTP, which binds well to cell-membrane barriers and enables translocation into the liver, is genetically fused to a human IFN-?, thereby enhancing the conjugation capacity of cell membranes and antiviral activity, inhibiting CTP transport into the cell nucleus, and enhancing the translocation and settlement of the fused protein into the liver and of transduction to the liver tissue. Accordingly, it is possible to develop protein-based medicines effective for preventing or treating various liver diseases associated with viral infection at low doses.

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

Abstract: Disclosed is a method of eliciting an immune response to an antigen present endogenously in a mammal. The method may comprise administering to the mammal a composition comprising at least one immunomodulator for inducing cell differentiation and or antigen-presenting function of antigen-presenting cell precursor. The antigen-presenting cell precursor may have taken up the antigen. Also disclosed are a composition for use in the method, an adjuvant comprising the composition, the use of the composition and the immunomodulator as described herein.

Abstract: This invention relates to use protein-polymer conjugates described in the specification to treat various diseases, including disease is idiopaic myelofibrsis, polycythaemia vera, and essential thromobocythaemia.

Abstract: Claimed and disclosed is a new use for a previously approved drug: erythropoietin. The present invention teaches using Erythropoetin to treat anemia caused by the combined treatment of Ribavirin and alpha-interferon. Erythropoetin has previously been approved for the treatment of anemia caused by cancer chemotherapy, renal failure and HIV. It has not been used for anemia caused by ribavirin. Ribavirin is part of a two-drug regimen now used to treat hepatitis C along with alpha interferon. The principal side effect of ribavirin is a hemolytic anemia. In the past, management of that anemia was done by dose reduction of the ribavirin, sometimes resulting in reversal of part of the anemia. It has become particularly important in light of new data, to maximize the dose of ribavirin given to persons undergoing treatment for hepatitis C to ensure a successful eradication of hepatitis C.

Abstract: The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula I, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising such compound admixed with at least one pharmaceutically acceptable excipient.

Abstract: Multifunctional polymers are disclosed having a smart segment and a biodegradable segment. Advantageously, the biodegradable segment includes a hydrophilic segment and a hydrophobic segment. Embodiments include combining the multifunctional polymeric material with a biologically active substance in an aqueous loading environment and administering the composition as a drug delivery vehicle to a human subject.

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

Abstract: Disclosed herein are methods for identifying compounds for the treatment of viral infection, including RNA viral infection and uses of the compounds as pharmaceutical compositions. The identified compounds modulate the RIG-I pathway in vertebrate cells.

Abstract: The disclosure relates to antigenic polypeptides that induce the production of opsonins, in particular opsonic antibodies, and the use of said antigenic polypeptides in vaccines that are protective against human bacterial pathogens.

Abstract: 2? and/or 3? prodrugs of 1?, 2?, 3? or 4?-branchednucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

Abstract: The present invention concerns multimeric complexes based on antibody fusion proteins comprising an AD moiety attached to the C-terminal end of each antibody light chain. The complexes further comprise effector moities attached to DDD moieties. Two copies of the DDD moiety form a dimer that binds to the AD moiety. The complexes may be trimers, pentamers, hexamers or other multimers. The effector moieties may be selected from a second antibody or antigen-binding fragment thereof, a cytokine, an interferon, a toxin, an antigen, a xenoantigen, a hapten, a protamine, a hormone, an enzyme, a ligand-binding protein, a pro-apoptotic agent and an anti-angiogenic agent. Surprisingly, attachment of the AD moiety to the C-terminal end of the antibody light chain results in improved pharmacokinetics and in vivo stability and efficacy, compared to homologous complexes wherein the AD moiety is attached to the antibody heavy chain.

Abstract: The present invention relates to interferon-?2b modified with Y-shaped branched polyethylene glycol (PEG) at a single Lys residue and the preparation thereof. The peglated IFN-?2b can be used for the preparation of a medicament for treating a disease, e.g. viral infections such as Hepatitis C.