Abstract: Provided are methods of producing mono- and di-pegylated IL-10.

Abstract: Methods for display of recombinant whole immunoglobulins or immunoglobulin libraries on the surface of eukaryote host cells, including yeast and filamentous fungi, are described. The methods are useful for screening libraries of recombinant immunoglobulins in eukaryote host cells to identify immunoglobulins that are specific for an antigen of interest.

Abstract: The present invention relates to the use of increased culture pH, relative to standard insect cell culture conditions, during baculovirus infection of lepidopteran insect cells to enable production of recombinant chikungunya (CHIKV) virus like particles (VLPs). The invention further relates to adapted insect cell lines derived from insect cells such as Sf21, which can grow robustly at elevated culture pH, the use of said cell lines to recombinantly produce pH sensitive proteins in the correct conformation and increase expression of recombinant proteins relative to standard insect cell lines. In some embodiments of the invention, the cells are useful for recombinant production of CHIKV VLPs. The invention also relates to a method for the production of a pH-adapted lepidopteran insect cell line. In some embodiments of said method, the cell line is produced and/or maintained in reduced phosphate serum-free insect cell media.

Abstract: The invention is directed to methods, reagents, and kits for the detection of MAPK/ERK pathway mutations in a patient diagnosed for cancer. In one embodiment, the invention comprises a sensitive and selective method to identify mutations to the BRAF, KRAS, and NRAS genes in a single reaction. In another aspect of this embodiment, the invention comprises primers and C probes for the detection of the BRAF, KRAS, and NRAS mutations using a single nucleotide primer extension assay. In another embodiment the invention is used to identify and select patients amenable for treatment with an ERK inhibitor.

Abstract: A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I: employing dynamic kinetic resolution (DKR). The DKR process involves an enzymatic enantioselective amination reaction catalyzed by transaminases. The process can be used to manufacture key intermediates in the preparation of poly (ADP-ribose) polymerase (PARP) inhibitors which may be useful for the treatment of cancer.

Abstract: The present invention relates to novel Fused Tetracycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, A?, B, G, R1, U, V, W, W?, X, X?, Y and Y? are as defined herein. The present invention also relates to compositions comprising at least one Fused Tetracycle Derivative, and methods of using the Fused Tetracycle Derivatives for treating or preventing HCV infection in a patient.

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Abstract: The invention provides compounds with enhanced permeability for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

Abstract: Compounds of Formula (I) are disclosed, wherein R1, R2, R3, R4, R5, and R18 are defined herein. The compounds encompassed by Formula (I) include compounds which are HCV NS5B inhibitors and other compounds which can be metabolized in vivo to HCV NS5B inhibitors. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract: Disclosed are the ERK inhibitors of Formula (I): (Formula (I)) and the pharmaceutically acceptable salts thereof. All substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of Formula (I).

Abstract: The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Abstract: The present invention provides novel pyrazole derivatives of formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Abstract: The present invention relates to different forms of a HCV inhibitory compound.

Abstract: The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Abstract: The present invention is directed to isoxazolopyndine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the isoxazolopyndine compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: In its many embodiments, the present invention provides certain S-imino-S-oxo iminothiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein RN, R1A, R1B, R2, R3, R4, ring A, RA, m, L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract: The present invention provides, inter alia, an isolated cell line, 3M as well as methods for making such a cell line and methods of using such a cell line, e.g., to produce a protein such as an immunoglobulin.

Abstract: In its many embodiments, the present invention provides certain S-imino-S-oxo iminothiadiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein RN, R1, R2, R3, R4, ring A, RA, m, L1, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract: The present invention is directed to substituted pyridizinone compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Abstract: In its many embodiments, the present invention provides certain C2-azaspiro substituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.