Abstract: The present invention relates to the complete biosynthetic pathway for the formation of the LL-F28249 compounds and, most importantly, the major component LL-F28249?. The purified and isolated nucleic acid molecule encoding the proteins of the biosynthetic pathway, which is isolated from a wild-type or mutant Streptomyces, is fully described in FIG. 6 to FIG. 6-39 and SEQ ID NO:1. The DNA gene cluster and its expression in a suitable host enable the efficient production of the highly active natural metabolites and semisynthetic derivatives. The invention further concerns plasmids, vectors and host cells that contain and express the novel nucleic acid molecule. Of particular interest, the entire biosynthetic pathway fits compactly in three plasmids, Cos11, Cos36 and Cos40. The invention also concerns the purified and isolated biosynthesis proteins that are encoded by the whole DNA gene cluster. Additionally, the invention involves a new efficient, biochemical method of preparing moxidectin.

Abstract: The present invention relates to methods for generating genetically modified and attenuated strains of vesicular stomatitis virus (VSV) for use in the preparation of immunogenic compositions. More particularly, the invention relates to the identification of particular genetic modifications of attenuated VSV that result in an increased yield of virus and an increase in stability of the attenuated strains for preparation of the immunogenic compositions. Methods for cell culture propagation and use in large scale production of VSV is also disclosed.

Abstract: An aqueous oral liquid pharmaceutical composition system with reduced propensity for agglomeration and phase separation which is particularly amendable to the suspension of one or more pharmaceutical actives that are substantially insoluble in water. The oral liquid pharmaceutical composition may further comprise pharmaceutical actives that are soluble in water and dissolve in the aqueous medium. In the composition of the invention both suspended and any dissolved active agents are distributed homogeneously.

Abstract: The present invention relates to novel 39-desmethoxy-39-methylrapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 39-desmethoxy-39-methylrapamycin derivatives in the treatment of cancer and/or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.

Abstract: An aminocarboxylic acid chelating agent, preferably EDTA, or a salt thereof has been found to be useful for inhibiting particulate formation in piperacillin/tazobactam parenteral combinations. The composition may also contain a buffer, preferably citrate, and optionally an aminoglycoside. The product may be in the form of a frozen composition that can be thawed for use. The product may also be in the form of a cryodesiccated powder that can be reconstituted by addition of an aqueous vehicle to reform a solution.

Abstract: The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds having the general structures below: which are useful in treating osteoporosis, acne, dysfunctional uterine bleeding, endometrial polyps, benign breast disease, adenomyosis, infertility, endometriosis, endometrial cancer, polycystic ovary syndrome, cardiovascular disease, Alzheimer's disease, cognitive decline, central nervous system disorders, central nervous system cancers, leukemia, endometrial ablations, chronic renal disease, chronic hepatic disease, coagulation diseases and disorders, hypocalcemia, hypercalcemia, Paget's disease, osteomalacia, osteohalisteresis, and multiple myeloma.

Abstract: Influenza virus-like particles (VLPs) comprising the structural proteins HA, NA, M1 and M2 are described. VLPs are also generated containing M1 alone, as are VLPs with M1 and any one or two of HA, NA and M2. VLPs with HA from one influenza subtype and NA from a different influenza subtype are also described, as are VLPs in which a portion or all of HA or NA is replaced by a heterologous moiety not produced by influenza virus, so as to comprise chimeric VLPs.

Abstract: The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor.

Abstract: The invention provides isolated nucleic acids molecules, designated PCIP nucleic acid molecules, which encode proteins that bind potassium channels and modulate potassium channel mediated activities. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PCIP nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PCIP gene has been introduced or disrupted. The invention still further provides isolated PCIP proteins, fusion proteins, antigenic peptides and anti-PCIP antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: A process for making a compound of formula I and intermediate compounds thereof, wherein R1 is CN, F or Cl; R2 is H or Br; and R3 and R4 are each independently H or F. The compounds of formula I are useful in the treatment of chronic inflammatory diseases, such as rheumatoid arthritis.

Abstract: This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2?). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

Abstract: The present invention provides a new composition for treating pain-associated sleep disturbances, especially shortened sleep duration, comprising ibuprofen and diphenhydramine. The composition is further prepared as a bilayer tablet or caplet, or alternatively as a soft gelatin capsule composition, to prevent interaction between the active ingredients.

Abstract: Estrogen receptor ligands, estrogen receptor polypeptide/ligand complexes, crystals of estrogen receptor polypeptide/ligand complexes, and related methods and software systems are disclosed.

Abstract: The present invention provides purified crystalline CCI-779 and processes for preparing the same.

Abstract: The present invention relates to modulators of metalloproteinase activity.

Abstract: A process is described for extracting gram-negative integral membrane proteins from bacteria or bacterial host cells containing a recombinant vector by differential detergent tangential flow diafiltration. This process has several advantages over alternate processes. First, it combines the clarification and extraction processes into one unit operation. The product is extracted from the cells and it is separated from cell debris with only one continuous diafiltration process. Second, the membrane proteins are extracted in a semi-purified state, which simplifies the downstream processing steps. Third, this process is very scalable because the only requirement is that the surface area of the membranes be increased proportionally with the amount of cells.

Abstract: The present invention is directed to compound of formula (A): wherein R1 is selected from (a) alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, or (b) CN and —C(NR10R11)?N—R12, R2 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl, R3-R12 are as described within the specification, and A is O, NR9 or S, or a prodrug, a pharmaceutically acceptable salt or a pharmaceutically active metabolite thereof, provided that R1 is not alkyl when R2 is pyridine, provided that at least one of R3-R8 is not H or F when A is O, R1 is (b) and R2 is a phenyl ring, a phenyl ring substituted at the para position with halo, —CN, —OCH3, —CF3 or —CO2CH3, a quinoline or an ethylene substituted with a phenyl ring or a 3,4-methylenedioxyphenyl moiety, provided that R4 is not methyl when R3 and R5-R8 are H, A is O, R1 is (b) and R2 is 4-chlorophenyl, and provided that R6 is not Cl when R3-R5 and R7-R8 are H, R1 is CN and R2 is phenyl.

Abstract: A method of treating gastroesophageal reflux disease (GERD), ulcers of the stomach or duodenum, or Zollinger-Ellison Syndrome in a human, by administering pantoprazole sodium multiparticulates is described. The pantoprazole multiparticulates have a spheroid core of pantoprazole or an enantiomer thereof, or a salt thereof, a surfactant, and a disintegrant; a sub coat which is comprised of hydroxypropyl methylcellulose (hypromellose) and water, an enteric coat on the subcoat, and a final seal coat over the enteric coat, which is composed of hydroxypropyl methylcellulose (hypromellose) and water.

Abstract: The present invention relates to the isolation and identification of two new strains of type 2B porcine circovirus. These two new strains of porcine circovirus may be used for the preparation of vaccine or immunogenic compositions for immunizing pigs against postweaning multisystemic wasting syndrome (PMWS). Accordingly, the invention provides methods for eliciting a protective immune response against a pathogenic porcine circovirus by administering to a pig an immunogenically effective amount of a type 2B porcine circovirus vaccine or immunogenic composition comprising at least one of the porcine circoviruses having a nucleic acid sequence as set forth in SEQ ID NOs: 1 or 2, or at least one protein from at least one of the two new type 2B strains of porcine circovirus as described herein. The invention further relates to protection of a pig from any one or more of the symptoms or sequelae associated with PMWS.

Abstract: Provided are certain methods of treating nonalcoholic fatty liver disease with farnesoid X receptor agonists. Also provided are certain methods of modulating levels of keratinocyte-derived chemokine (KC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cytokeratin 18 (CK-18), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-14 (MMP-14), tissue inhibitor of metalloproteinase 1 (TIMP-1), and Cytochrome P450 2E1 (CYP2E1); certain methods of identifying FXR modulators; and certain methods of treating patients with existing cholesterol gallstone disease.