Abstract: The present invention provides genetic markers and biomarkers that are associated with anemia induced by ribavirin therapy. The genetic markers are located in the ITPA gene and elsewhere on human chromosome 20 and the biomarkers are low ITPA activity phenotypes. These markers of ribavirin-induced anemia are useful, inter alia, to identify patients who are least likely to develop anemia upon treatment with ribavirin pharmaceutical compositions and drug products, in methods of treating patients having a disease susceptible to treatment with ribavirin, and in methods for selecting the most appropriate therapy for such patients.

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: Methods and compositions for reducing fibrosis and cirrhosis are provided in which an effective dose of an admixture of a polysaccharide compound and, for example, a compound selected from the group consisting of antibodies specific to intracellular or cell-surface: (i) beta-PDGF receptors; (ii) synaptophysin; (iii) zvegf3; (iv) CCR1 receptors; (v) connective tissue growth factor; (vi) alpha 1-smooth muscle actin; (vii) matrix metalloproteinases MMP 2 and MMP9; (viii) matrix metalloproteinase inhibitors TIMP1 and TMP2; (ix) integrins; (x) TFG-?1; (xi) endothelin receptor antagonists; and (xii) collagen synthesis and degradation modulating compounds; (xiii) actin synthesis and degradation modulating compounds; and (xiv) tyrosine kinases is administered to an animal in order to treat fibrosis.

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 stereoselective 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: New chiral and achiral oxy-substituted cyclopentyl pyridinone diketocarboxamides and their derivatives and methods for their preparations are disclosed. The compounds include tautomers, regioisomers and geometric isomers. These complex carboxamides are designed as inhibitors of HIV replication through inhibition of HIV integrase. The compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

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: A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV.

Abstract: Clemizole and clemizole analog compounds, and pharmaceutical compositions of the same, are useful in methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of inhibiting HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3?UTR of HCV negative strand RNA in a host, and methods of treating liver fibrosis in a host.

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: The present invention discloses a new class of compounds that exhibit an inhibitory effect on influenza virus type A and B, which may or may not be resistant to other drugs, as well as on other types of viruses, such as flavivirus but also on protozoa and other micro-organisms, their preparation methods, pharmaceutical formulations containing them and their use as medicinal products for the treatment of various conditions caused by particular microorganisms, including viruses, bacteria and protozoa, which affect animal and human health.

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H? function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

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: This invention provides a recombinant super-compound interferon or an equivalent thereof with changed spatial configuration. The super-compound interferon possesses anti-viral or anti-tumor activity and, therefore, is useful in preventing and treating viral diseases and cancers. This invention also provides an artificial gene which codes for the super-compound interferon or its equivalent. Finally, this invention provides methods for producing recombinant super-compound interferon or its equivalent and various uses of said interferon.

Abstract: The present invention provides novel peptide immunogens comprising influenza virus matrix 2 protein epitopes and related compositions and methods. The present invention relates to a composition comprising a peptide immunogen useful for the prevention and treatment of an influenza virus-mediated disease. The invention also relates to vaccines, immunogenic products and immunogenic compositions containing the peptide immunogens.

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 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: The present invention provides novel immunotherapeutic compositions and methods useful for treating or preventing microbial infections, weakened immune systems, diseases in which cells have become obligately anerobic and cellular proliferative disorders including cancer. The immunotherapeutics herein use benzaldehyde derivatives, precursors and intermediaries alone or in combination with additional therapeutic agents to stimulate the immune system and inhibit cellular proliferation.

Abstract: A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV.

Abstract: Specific binding members that bind the ED-A isoform of fibronectin for use in methods of diagnosis, detection, imaging and/or treatment of inflammatory bowel disease such as ulcerative colitis and/or for use in delivery to the neovasculature of intestinal tissue of a molecule conjugated to the specific binding member. Specific binding members that bind tenascin-C, especially the A1, A2, A3, A4 and/or D domain tenascin-C large isoform, for use in methods of diagnosis, detection, imaging and/or treatment of ulcerative colitis and/or for use in delivery to the neovasculature of inflammatory bowel disease tissue of a molecule conjugated to the specific binding member.

Abstract: Disclosed herein are methods for the treatment of cancer and inflammatory-based diseases and disorders, such as hepatitis B virus infection based upon the administration of calcium pterin. In one embodiment is a method of treating cancer comprising administration of dipterinyl calcium pentahydrate (DCP). In another embodiment is a method of treating hepatitis B virus infection comprising administration of dipterinyl calcium pentahydrate (DCP).

Abstract: The embodiments provide compounds of the general Formula I, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further 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: 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 comprises a new combination or association of pharmacologically active substances and/or non-drug treatments for chronic systemic diseases such as cancer. According to the present invention, the combination or association of substances and/or non-drug treatments is used to treat cancer, clinical problems associated to cancer and adverse side effects related to substances and/or treatments used to fight this illness. The components of the combination or association of substances, the biological response modifier (proteic aggregate of ammonium and magnesium phospholinoleate-palmitoleate anhydride) and at least one substance and/or treatment with antineoplastic properties can be jointly or simultaneously or consecutively or sequentially administered in an appropriate form, according to their chemical properties, and with the use of the most suitable procedures, and also in the most therapeutically effective dose and use.

Abstract: Ezatiostat is useful for inhibiting multiple myeloma cell proliferation and treating multiple myeloma, alone or when added together with another anti-myeloma drug.

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 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: This invention relates to novel compounds that are peptides derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel peptides that are deuterated derivatives of boceprevir. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating HCV infection.

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: 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 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 invention relates to 2?-allene-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

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: The present invention provides IFN-? conjugates including IFN-? peptides and modifying groups such as PEG moieties. The IFN-? peptide and modifying group are linked via an intact glycosyl linking group interposed between and covalently attached to the IFN-? peptide and the modifying group. The IFN-? conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar onto an amino acid or a glycosyl residue on the IFN-? peptide. Also provided are methods for preparing the IFN-? conjugates, methods for treating various disease conditions with the IFN-? conjugates, and pharmaceutical formulations including the IFN-? conjugates.

Abstract: The present invention relates to 5,6-ring annulated indole derivatives of the formula (I), compositions comprising at least one 5,6-ring annulated indole derivatives, and methods of using the 5,6-ring annulated indole derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

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: 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 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: 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 disclosure provides a biodegradable drug delivery composition including a vehicle and an insoluble component comprising beneficial agent dispersed in the vehicle. Typically, the composition is not an emulsion, but has a low viscosity and further provides for minimized initial burst and sustained release of the beneficial agent over time. Also provided, are kits including the biodegradable drug delivery composition or components thereof, as well as methods of making and using the biodegradable drug delivery composition.

Abstract: Antibodies that bind CSF1R are provided. Antibody heavy chains and light chains that are capable of forming antibodies that bind CSF1R are also provided. Polynucleotides encoding antibodies to CSF1R are provided. Polynucleotides encoding antibody heavy chains and lights chains are also provided. Methods of treatment using antibodies to CSF1R are provided. Such methods include, but are not limited to, methods of treating rheumatoid arthritis, bone loss, and multiple sclerosis.

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 invention provides compounds of formula I, II, and III as described herein, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates that are useful for preparing the compounds. The compounds of formula I, II, and III are useful as anti-viral agents and/or as anti-cancer agents.

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: Antisense oligomers useful for modulating hepatitis B virus infections, and for the treatment of hepatitis B virus (HBV) and hepatitis B virus-related conditions in animals including humans. More particularly, antisense oligomers with modified nucleotides for treatment of HBV in animals, more particularly antisense oligomers comprising 2?O-4?C-methylene-bridged sugars, or nucleotides with other 2?O-4?C bridged sugars, also known as locked nucleic acids (LNA), for treatment of HBV in animals, and more particularly for treatment of HBV in humans.

Abstract: The present invention is directed to methods of producing conjugates of A? peptide immunogens with protein/polypeptide carrier molecules, which are useful as immunogens, wherein peptide immunogens are conjugated to protein carriers via activated functional groups on amino acid residues of the carrier or of the optionally attached linker molecule, and wherein any unconjugated reactive functional groups on amino acid residues are inactivated via capping, thus retaining the immunological functionality of the carrier molecule, but reducing the propensity for undesirable reactions that could render the conjugate less safe or effective. Furthermore, the invention also relates to such immunogenic products and immunogenic compositions containing such immunogenic products made by such methods.

Abstract: The disclosure provides compounds of formula I, including their 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: 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.

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: The present invention relates to the use of spinosyns and spinosyn compositions as pharmaceuticals and methods for treatment—including prevention—of protozoan infections and/or disorders relating to a protozoan infection, such as malaria and leishmania, viral infections such as Herpes Simplex virus and Influenza virus and neoplastic disorders or cancer. Advantageously, compositions of the invention inhibit protozoan, virus growth and neoplastic cell proliferation with only minimal or no disruption or ham to the host which may be an animal or human.

Abstract: Methods of stimulating or enhancing an immune response in a host are disclosed. The methods include contacting a monocyte with 15 kD granulysin thereby producing a monocyte-derived dendritic cell. In one example, the method further includes contacting the monocyte or monocyte-derived dendritic cell with a target antigen, such as a tumor antigen or an autoimmune antigen. In another embodiment, the method includes contacting the monocyte with an additional agent that enhances maturation of dendritic cells or induces immunological tolerance. The methods are of use in vivo, in vitro and ex vivo. In another aspect, the disclosure relates to compositions and methods for the treatment of tumors.