Abstract: The present invention relates to a novel antiviral product, its use in the treatment of hepatitis C, and its process of manufacture. More particularly it relates to a characterised product exhibiting antiviral activity against Hepatitis C virus (HCV). In one embodiment there is provided a single herb Astragalus extract, or an active fraction thereof, for use as an antiviral in the treatment of hepatitis C.

Abstract: The present specification discloses beta-amino alcohols and methods of treating a neurodegenerative disease using such compounds.

Abstract: The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein at least one bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Abstract: Compounds of formula (I): wherein B, X, R3, L0, L1, L2, R2, R1 and RC are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

Abstract: A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.

Abstract: The present invention relates to compositions, methods and kits based on the ADAM-mediated cleavage of Her-2. The present invention also relates to treatments for cancer, and in particular, breast cancer, by modulating the ADAM-mediated cleavage of Her-2. Further, the invention relates to compositions, methods and kits based on the surprising synergistic effect between inhibition of Her-2 cleavage by an ADAM and certain cytostatic (e.g., Herceptin) and cytotoxic (e.g., Taxol) compounds in, among other things, inhibiting tumor cell proliferation and inducing cell death. Additionally, the invention relates to novel variants of ADAM15, designated ADAM15 variant 1 and ADAM15 variant 2, now identified and isolated.

Abstract: Provided are compounds of Formula I: nucleosides, nucleoside phosphates and prodrugs thereof, wherein R6 is CN, ethenyl, 2-haloethen-1-yl, or (C2-C8)-alkyn-1-yl. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections.

Abstract: Disclosed are combinations comprising (a) a compound of the Formula: wherein R1, R2, R7, R8, R9 and W are as defined in the specification, and (b) at least one additional therapeutic agent. Such combinations are useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, and inflammatory conditions in mammals. Also disclosed are methods of using such combinations in the treatment of hyperproliferative diseases and inflammatory conditions in mammals.

Abstract: The present invention relates to novel Linked Tricyclic Aryl Compounds, compositions comprising at least one Linked Tricyclic Compound, and methods of using Linked Tricyclic Aryl Compounds for treating or preventing HCV infection in a patient.

Abstract: The present invention provides new pyridopyrazine compounds which are suitable for the treatment or prevention of physiological and/or pathophysiological states mediated and/or modulated by signal transduction pathways and/or enzymes in mammals and in particular in humans.

Abstract: Methods and pharmaceutical compositions for treating viral infections, by administering certain 2-aryl-benzothiazole or 2-heteroaryl-benzothiazole derivative compounds in therapeutically effective amounts are disclosed. Methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by flavivirus is disclosed, i.e., including but not limited to, Dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus.

Abstract: A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

Abstract: The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

Abstract: The present invention provides new pyridopyrazine compounds which are suitable for the treatment or prevention of physiological and/or pathophysiological states mediated and/or modulated by signal transduction pathways and/or enzymes in mammals and in particular in humans.

Abstract: The present invention provides an ex vivo method of treating plasmacytoid dendritic cells (pDC) in Th2- or Th17-associated diseases by modulating the cytokine expression or secretion using interferon lambda (IFN-?). For the Th-2 or Th17-associated diseases, pDC cells from a patient having the disease are exposed ex vivo with IFN-? in an effective amount to inhibit cytokine releases. The IFN-? exposed pDC are administered back into the patient. The present invention also provides a method of ex vivo IFN-? treatment of pDC, in conjunction with co-administration of a composition comprising IFN-?.

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

Abstract: The present invention relates to novel Fused Tricyclic Aryl Compounds, compositions comprising at least one Fused Tricyclic Aryl Compound, and methods of using the Fused Tricyclic Aryl Compounds for treating or preventing HCV infection in a patient.

Abstract: Provided are a triterpene derivative represented by a general formula (I), a pharmaceutically acceptable salt thereof, and an agent for preventing or treating chronic hepatitis C comprising the triterpene derivative or the salt as an active ingredient: [in the formula (I), R1 represents a carboxyl group, a hydroxymethyl group, —CH2OSO3H, or and R2 represents —OR3 or —O— (CH2) m-OR4, where R3 represents a benzyl group which may be substituted with a hydroxymethyl group, a dimethylaminomethyl group, a phenylaminomethyl group, a morpholinomethyl group, a carboxyl group, or a formyl group, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, or a hydroxy C1-6 alkyl group, R4 represents a phenyl group which may be substituted with a carboxyl group, and m represents an integer of 1 to 3, with the proviso that a case where R1 is —CH2OH, and R3 is a C1-6 alkyl group, a C2-6 alkenyl group, or a benzyl group is excluded].

Abstract: A synergistic adjuvant is provided comprising synergistically effective amounts of at least one type 1 interferon and at least one CD40 agonist, wherein these moieties may be in the same or separate compositions. In addition, fusion proteins and DNA conjugates which contain a type 1 interferon/CD40 agonist/antigen combination are provided. The use of these compositions, protein and DNA conjugates as immune adjuvants for treatment of various chronic diseases such as HIV infection and for enhancing the efficacy of vaccines (prophylactic and therapeutic) is also provided.

Abstract: A prophylactic or therapeutic agent for a viral disease, characterized by combining 22?-methoxyolean-12-ene-3?,24(4?)-diol with an interferon as active ingredients is disclosed. The prophylactic or therapeutic agent of the present invention exhibits a high therapeutic effect by administering 22?-methoxyolean-12-ene-3?,24(4?)-diol and interferon as a combination 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 target 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 target agents and one PEG moiety. In alternative embodiments, the target 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 target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. 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 relates inter alia to the treatment or prevention of influenza virus infection (including subtypes influenza A virus, influenza B virus, avian strain H5N1, A/H1N1, H3N2 and/or pandemic influenza) using compounds which inhibit the activity of p59-HCK and to a method of screening for a candidate drug substance intended to prevent or treat influenza virus infection in a subject, said method comprising identifying a test substance capable of inhibiting p59-HCK activity.

Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Abstract: The present invention includes therapeutic methods that include the administration of a compound of Formula I or II: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, to a subject in need of such, and therapeutic methods that include the administration of such compounds with at least one additional active agent.

Abstract: The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: Novel heterocyclic derivatives of formula (I): or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein Ra, n, R1 and R2 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5).

Abstract: The present invention provides a method for treating multiple sclerosis (MS), and for reducing flu-like symptoms associated with administration of an interferon to a patient with MS. The method involves intramuscularly administering the interferon to the MS patient according to an escalating dosing regimen in weeks 1 to 3, and a full therapeutically effective dose of interferon in week 4. In one embodiment of the invention, the escalating dosing regimen comprises administering one quarter of the therapeutically effective dose in week 1, half of the therapeutically effective dose in week 2, and three-quarters of the therapeutically effective dose in week 3. Also provided are titration packages for enabling compliance with a regimen of changing dosage of an interferon over a period of time.

Abstract: The present invention concerns compositions and use of multivalent and/or multispecific antibodies or immunoconjugates, preferably made by the dock-and-lock technique. The antibodies or immunoconjugates may comprise a first and second polypeptide, each comprising VH and VL domains in series, wherein the first and second polypeptides bind to each other, wherein a VH domain on one polypeptide binds to a complementary VL domain on the other polypeptide to form an antigen binding site, wherein VH and VL domains on the same polypeptide do not bind to each other and wherein one polypeptide is attached to the amino terminal end of a CH1 domain and the other polypeptide is attached to the amino terminal end of a CL domain. The carboxyl terminal end of the CH1 domain may be attached to a CH2-CH3 domain. The antibodies or immunoconjugates are of use to treat a wide variety of 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: Provided are methods for detecting bladder cancer in a subject. In some aspects, methylation of one or more of MYO3A, CA10, NKX6-2, SOX11, DBC1, NPTX2, and/or A2BP1 in DNA sediment from a urine sample may be evaluated to detect the presence or absence of a bladder cancer in a human patient.

Abstract: The present invention provides 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 compositions and methods for the preparation, stabilization, and/or storage of active agents, particularly therapeutic proteins and polypeptides such as Interleukin-2.

Abstract: The present invention provides compositions comprising isolated human collagen, isolated human elastin and a pharmaceutically acceptable carrier wherein the human elastin is substantially insoluble in water with a molecular weight greater than 100 kDa. The present invention further provides methods and kits for soft tissue augmentation.

Abstract: The present disclosure generally relates to crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide. The present disclosure also generally relates to a pharmaceutical composition comprising one or more of the crystalline forms, as well of methods of using the crystalline forms in the treatment of Hepatitis C virus (HCV) and methods for obtaining such crystalline forms.

Abstract: Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases are disclosed, using multispecific antagonists that target at least two different markers. The different targets are proinflammatory effectors of the innate immune system. The multispecific antagonists can be used to treat sepsis or septic shock.

Abstract: Disclosed are pharmaceutical combinations comprising at least one S1P receptor agonist, as well as a method for treating demyelinating diseases, e.g. multiple sclerosis or disorders associated therewith or Guillain-Barré syndrome, comprising co-administration, e.g. concomitantly or in sequence, of a therapeutically effective amount of a) an S1P receptor agonist, and b) at least one co-agent shown to have clinical activity against at least one symptom of a demyelinating disease.

Abstract: The present invention concerns methods and compositions for PEGylated complexes of defined stoichiometry and structure. Preferably, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and a PEG moiety to an AD sequence, 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. Alternatively, 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 relates to skin care compositions, including cosmeceuticals, for topical application, and more particularly, a skin cream, comprising cell culture medium conditioned by cells grown in two-dimensional culture. Also included are methods of using such compositions and kits comprising the skin cream therein.

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: A method of treating tuberculosis comprising administering an aerosolized interferon such as interferon ?, interferon ? or interferon ? in a therapeutically effective amount is provided herein. Further, a method of reducing the infectivity of tuberculosis or reducing the number of infectious organisms present in the lungs of a patient suffering from tuberculosis comprising administering an aerosolized interferon such as interferon ?, interferon ? or interferon ? in a therapeutically effective amount is provided herein. Also, pharmaceutical compositions of one or more aerosolized interferon(s) are provided.

Abstract: The present invention provides novel substituted quinoline compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: This invention relates to targeted delivery of anti-viral compounds through protein bioconjugation. More particularly, it relates to an anti-viral compound conjugated to a protein, such as hemoglobin and to a method of treating a viral infection using said conjugate. The invention also provides a method of targeted drug delivery of an anti-viral nucleoside analogue to macrophages, cells comprising a hemoglobin receptor and to CD163 bearing cells.

Abstract: The invention relates to a method and kit for treating cancer in a human subject, the method comprising administering to the subject in combination therapeutically effective amounts of a VEGF-C antagonist and an anti-neoplastic composition, and the kit comprising a VEGF-C antagonist for administering to the subject in combination with an anti-neoplastic composition. The invention further relates to methods for: increasing the duration of survival of, increasing the progression-free survival of, increasing the duration of response of, or treating, a subject or a group of human subjects susceptible to or diagnosed as having a cancer; or treating a human subject or a group of human subjects having metastatic colorectal cancer, prostate cancer, pancreatic cancer or glioblastoma, the methods comprising administering to the subject or subjects in the group in combination effective amounts of a VEGF-C antagonist and an anti-neoplastic composition.

Abstract: Described herein is the identification of genes that are significantly up- or down-regulated in patients suffering from cancer-related fatigue (CRF), providing a means for the diagnosis and treatment of CRF. In particular, provided herein is a method of diagnosing a subject with CRF by detecting expression of at least one gene associated with CRF in a sample obtained from the subject; and comparing expression of the at least one gene to a control. Also described herein is a method of treating a patient with CRF by administering to the subject an agent that alters expression or activity of a gene associated with CRF. Further provided is array that includes a plurality of genes associated with CRF, such as TNFRSF25, SLC6A8, OGT, SNCA, APBA2, CASK, OR2W3, MYL4, IL7R, ARHGEF10 and ITGA6.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula I, and pharmaceutical compositions 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: A composition which includes a carboxamide, preferably ribavirin, for treating viral diseases in humans. A preferred embodiment of the subject invention comprises a very high dose (>600 mg) of ribavirin, and more preferably between about 800-1200 mg of ribavirin or more per dosage form.

Abstract: Methods for treating multiple sclerosis (MS) with a CD20 antibody using special dosing regimens and protocols are described. Articles of manufacture for use in such methods are also described.

Abstract: The present invention relates to methods for predicting and evaluating metastasis of solid cancers, such as melanoma, in a subject by measuring serum biomarkers associated with a metastatic phenotype. In particular, the present invention provides a serum gene expression signature that is different between highly aggressive and more metastatic versus less aggressive and less metastatic melanomas by quantitatively measuring the levels of, inter alia, lymphoid-specific helicase (HELLS) and condensing complex subunit 2 (NCAPH) transcripts in a subject.