Abstract: The present invention provides nucleoside phosphoramidate compounds of Formula I, where R1, R2a, R2b, R3, R4, R5a, R5b, R6, R7, R8a, R8b, M and W are as defined herein. The invention further includes pharmaceutical compositions comprising a compound of Formula I, methods of use of these compounds for treating a viral infection, and methods of producing these compounds.

Abstract: A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, B, Z, M, W and n 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 for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: New imidazo[1,2-b]pyridazine and imidazo[4,5-b]pyridine 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: The present invention relates to the use of an R-enantiomer of a compound according to the following formula (I) (I), wherein R1 or R2 is a group selected from H, —CH3, —CH2CH3, —CH2CH2CH3, and —CH2CH2CH2CH3 or can be taken together with another to give a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring, or a cyclohexyl ring, R3 is a group selected from —COOH, —COOR6, —CONH2, —CONHR6, —CONR6R7, —CONHSO2R6, —COO—(CH2)3—CH2OH, —COO—(CH2)4—ONO2, —COO—PhOCH3—C2H2—COO—(CH2)4—ONO2, tetrazolyl, and a —COOH bioisostere, R4 or R5 is a group selected from —Cl, —F, —Br, —I, —CF3, —OCF3, —SCF3, —OCH3, —OCH2CH3, —CN, —CH?CH2, —CH2OH, and —NO2, R6 of R7 is a group selected from —CH3, —CH2CH3, —CH2CH2CH3, and —CH2CH2CH2CH3, and m or n is an integer selected from 0, 1, 2, and 3, or a nitro-variant of said compound, and pharmaceutically acceptable salts of said compound, preferably Tarenflurbil (R-Flurbiprofen), for use in the treatment of multiple sclerosis (MS).

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Abstract: Disclosed are compositions and methods comprising combinations of anti-CD74 antibodies with a therapeutic agent that is attached to the anti-CD74 antibody or separately administered. Preferably, the therapeutic agent is an antibody that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 or HLA-DR. However, the therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 antibody is part of a DNL complex. More preferably, combination therapy with the anti-CD74 antibody and therapeutic agent is more effective than antibody alone, therapeutic agent alone, or the combination of unconjugated anti-CD74 antibody and therapeutic agent. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes.

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 relates to vaccines comprising at least one mRNA encoding at least one antigen for use in the treatment of a disease in an elderly patient preferably exhibiting an age of at least 50 years, more preferably of at least 55 years, 60 years, 65 years, 70 years, or older, wherein the treatment comprises vaccination of the patient and eliciting an immune response in said patient. The present invention is furthermore directed to kits and kits of parts comprising such a vaccine and/or its components and to methods applying such a vaccine or kit.

Abstract: Methods of treating neurological disorders, e.g., those characterized by demyelination and/or axonal loss (e.g., MS), are provided. The methods comprise administration of a therapeutically effective amount of at least one compound of Formula I: wherein R1 and R2 are independently selected from OH, O?, and (C1-6)alkoxy, or a pharmaceutically acceptable salt thereof; and either glatiramer acetate or interferon-beta.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: The present invention discloses administering steroid hormones to mammals to treat autoimmune related diseases, more particularly, Th1-mediated (cell-mediated) autoimmune diseases including: multiple sclerosis (MS), rheumatoid arthritis (RA), autoimmune thyroiditis and uveitis. Most preferably the invention is used to treat a patient with a therapeutically effective amount of estriol of 8 milligrams once daily via oral administration to treat the symptoms or prevent the onset of multiple sclerosis.

Abstract: The subject invention provides for methods of reducing the relapse rate and/or reducing the accumulation of physical disability in a relapsing-remitting multiple sclerosis human patient, the method comprising orally administering to the patient a daily dose of 0.6 mg laquinimod. The subject invention also provides for pharmaceutical oral unit dosage forms of 0.6 mg laquinimod for use in reducing the relapse rate and/or for use in reducing the accumulation of physical disability in a relapsing-remitting multiple sclerosis human patient.

Abstract: Disclosed are Fc-interferon-beta (Fc-IFN-?) fusion proteins and nucleic acid molecules encoding them. The Fc-IFN-? fusion proteins include variants of the interferon-beta (IFN-?) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and/or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

Abstract: A composition including a surfactant and at least one alkyl glycoside and/or saccharide alkyl ester and a drug. The surfactant composition(s) when admixed with a drug is non-toxic and non-irritating, while stabilizing and increasing the bioavailability of the drug. The invention also provides compositions that enhance absorption of drugs via the oral, ocular, nasal, nasolacrimal, inhalation or pulmonary, oral cavity (sublingual or Buccal cell) or CSF delivery route of a patient, including but not limited to insulin, glucagon and exendin-4.

Abstract: Modulators of CRTH2, particularly antagonists of CRTH2, that are useful for treating various disorders, including asthma and respiratory disorders are disclosed.

Abstract: The invention is directed to 3,5-disubstituted and 3,5,7-trisubstituted-3H-oxazolo and 3H-thiazolo[4,5-d]pyrimidin-2-one compounds and prodrugs thereof that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and pharmaceutical compositions containing them, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds and prodrugs.

Abstract: The invention relates to an immunity-inducing agent comprising, as an active ingredient, at least one polypeptide having immunity-inducing activity that is selected from among polypeptides (a), (b), and (c): (a) a polypeptide of at least seven contiguous amino acids of the amino acid sequence shown by any even SEQ ID number selected from SEQ ID NOs: 2 to 30 listed in the Sequence Listing; (b) a polypeptide of at least seven amino acids having 90% or more sequence identity with the polypeptide (a); and (c) a polypeptide comprising the polypeptide (a) or (b) as a partial sequence thereof, or a recombinant vector comprising a polynucleotide encoding said polypeptide and capable of expressing said polypeptide in vivo.

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 disclosure relates to methods of using fatty acid amide hydrolase (FAAH) inhibitors alone or in combination for the treatment or prevention of abdominal, visceral or pelvic pain. Also described herein are pharmaceutical compositions comprising a FAAH inhibitor, alone or in combination with an additional therapeutic agent for the treatment of abdominal, visceral or pelvic pain.

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: New imidazopyridine 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: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contact with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Abstract: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Abstract: Methods of using azide-modified biomolecules, such as fatty acids, carbohydrates and lipids, to treat a plant, an insect or an animal infected with a virus or to inhibit infectivity of a virus, such as the human immunodeficiency virus, are provided. Also provided are methods of labeling a virus, such as human immunodeficiency virus, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. Also, provided are methods of tracking a virus in vivo, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. The azide-modified biomolecules may be combined with a pharmaceutically acceptable excipient to produce a pharmaceutical composition, optionally containing another anti-viral agent and/or a delivery agent, such as a liposome.

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: 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 a tyrosine kinase inhibitor or a mast cell inhibitor, and in particular masitinib or a pharmaceutically acceptable salt thereof, for the treatment of human multiple sclerosis.

Abstract: The disclosure relates to a vaccine including at least one adjuvant useful in the prevention and treatment of blood cancers, for example lymphoma, leukaemia or myeloma.

Abstract: Disclosed herein are compositions and methods of use comprising combinations of anti-CD22 antibodies with a therapeutic agent. The therapeutic agent may be attached to the anti-CD22 antibody or may be separately administered, either before, simultaneously with or after the anti-CD22 antibody. In preferred embodiments, the therapeutic agent is an antibody or fragment thereof that binds to an antigen different from CD22, such as CD 19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80 and HLA-DR. However, the therapeutic agent may an immunomodulator, a cytokine, a toxin or other therapeutic agent known in the art. More preferably, the anti-CD22 antibody is part of a DNL complex, such as a hexavalent DNL complex. Most preferably, combination therapy with the anti-CD22 antibody or fragment and the therapeutic agent is more effective than the antibody alone, the therapeutic agent alone, or the combination of anti-CD22 antibody and therapeutic agent that are not conjugated to each other.

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: [PROBLEMS] To provide a technique which enables an effective antibody therapy for cancer which targets for FGFR1 without the need of using any effective antibody having high specificity and a potent cell-killing activity. [MEANS FOR SOLVING PROBLEMS] Disclosed are: a therapeutic agent for cancer, which comprises an enhancer of the expression of a fibroblast growth factor receptor-1 and an anti-fibroblast growth factor receptor-1 antibody; and a method for the treatment of cancer using the therapeutic agent.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a carrier such as a polymer, nanoparticle, complex or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing cell death of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate.

Abstract: Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8+ memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity.

Abstract: This invention is related to the use of the combination of teriflunomide and interferon beta thereof, for the preparation of a medicament for use in treating multiple sclerosis.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Abstract: The present invention relates to Macrophage Activating Factors such as GcMAF and compositions thereof, for use in the treatment of a patient suffering from CFS/ME and/or XMRV infection.

Abstract: The present invention describes method of treating bacterial infections, including MRSA. In various embodiments, the methods can use interferon beta, which is found to have antimicrobial activity. In certain embodiments, the interferon beta can be human interferon beta. In other embodiments, the interferon beta can be mouse interferon beta. In further embodiments, the interferon beta can be human interferon beta containing amino acid substitutions to make the human interferon beta more cationic in neutral pH.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19VH sequence.

Abstract: Methods, compositions and articles of manufacture for contributing to the treatment of cancers, including solid tumors, are disclosed. The methods, compositions and articles of manufacture can utilize an endothelin B agonist (ETB) to enhance the delivery and resulting efficacy of a chemotherapeutic agent.

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: 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: Disclosed are compositions that include anti-CD74 immunoconjugates and a therapeutic and/or diagnostic agent. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. The compositions may be part of a kit for administering the anti-CD74 immunoconjugate compositions in therapeutic and/or diagnostic methods.

Abstract: Disclosed is a method of administering an interleukin-2 receptor (IL-2R) antagonist to a subject to treat an autoimmune disease. In particular embodiments, the IL-2R antagonist is an anti-IL-2R monoclonal antibody specific for one or more chains of the IL-2R, such as the alpha-chain, for example daclizumab. In other particular embodiments the autoimmune disease is multiple sclerosis. In certain embodiments administration of interferon-beta is combined with administration of an antagonist of the IL-2R to provide significant clinical improvement in a subject with an autoimmune disease.

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections.

Abstract: A method is provided for determining the efficacy of interferon-beta (IFN-?) therapy in a subject with multiple sclerosis. One step of the method can include obtaining a biological sample from the subject. After obtaining the biological sample, the expression level of at least one interferon-regulated gene (IRG) and/or variant thereof can be determined. Increased or decreased expression of the at least one IRG and/or variant thereof as compared to a control may indicate that the subject will respond poorly to IFN-? therapy.

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

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKK?/? and I?B?, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Abstract: The present invention relates to 2?-chloroacetylenyl-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.