Abstract: Compositions and formulations comprising N-glycosylated insulin analogues are described. In particular embodiments, the glycosylated insulin analogues are produced in vivo and comprise one or more the N-linked N-glycans selected from high mannose or fucosylated or non-fucosylated hybrid, paucimannose, or complex N-glycans. In other embodiments, the N-glycan comprising the high mannose or fucosylated or non-fucosylated hybrid, paucimannose, or complex N-glycan is attached to the insulin analogue in vitro. Examples of N-glycans include but are not limited to a molecule having a structure selected from N-glycans in the group consisting of Man(1—9)GlcNAc2; or selected from N-glycans in the group consisting of GlcNAc(1—4)Man3GlcNAc2; or selected from N-glycans in the group consisting of Gal(j.

Abstract: A drug delivery system consisting of one or more compartments and comprising a progestogenic compound dissolved in a thermoplastic polyethylene vinylacetate copolymer whereby, if the delivery system consists of one compartment, the compartment comprises (i) a core of a thermoplastic polyethylene vinylacetate copolymer comprising the progestogenic compound, such progestogenic compound being dissolved in the polyethylene vinylacetate copolymer up to a concentration below the saturation level at 25° C., and an estrogenic compound; and (ii) a skin of a thermoplastic polyethylene vinylacetate copolymer covering the core, said skin being permeable for both compounds; if the delivery system consists of more than one compartment, only one compartment comprises (iii) the progestogenic compound, such progestogenic compound being dissolved in a core of a thermoplastic polyethylene vinylacetate copolymer up to a concentration below the saturation level at 25° C.

Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more disease associated with the central nervous system using such compounds or pharmaceutical compostions.

Abstract: Glucagon receptor antagonist compounds are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Abstract: Interleukin-10 (IL-10) conjugated via a linker to one or more polyethylene glycol (PEG) molecules at a single amino acid residue of the IL-10, and a method for preparing the same, are provided. The method produces a stable mono-pegylated IL-10, which retains IL-10 activity, where pegylation is selective for the N-terminus on one subunit of IL-10 with little or no formation of monomeric IL-10. The method also provides a substantially homogenous population of mono-PEG-IL-10.

Abstract: Described is a method for increasing the N-glycosylation site occupancy of a therapeutic glycoprotein produced in recombinant host cells modified as described herein and genetically engineered to express the glycoprotein compared to the N-glycosylation site occupancy of the therapeutic glycoprotein produced in a recombinant host cell not modified as described herein. In particular, the method provides recombinant host cells that overexpress a heterologous single-subunit oligosaccharyltransferase, which in particular embodiments is capable of functionally suppressing the lethal phenotype of a mutation of at least one essential protein of the yeast oligosaccharyltransferase (OTase) complex, for example, the Leishmania major STT3D protein, in the presence of expression of the host cell genes encoding the endogenous OTase complex.

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract: Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalkyl substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalkyl substituent connected directly to the ring or attached to the ring through a —CH2—.

Abstract: The invention provides certain amino-pyridine-containing compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and n are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.

Abstract: Diaphragm valve with internal leak detection and improved external leak sealing performance. In diaphragm valves comprising diaphragms that have shields and backings, a rigid seal plate interposed between the shield and backing prevents peripheral regions of the shield from cold-flowing into the backing, despite the compression forces produced by tightening the fasteners that secure the diaphragm to the valve's bonnet assembly and body. An access port passing through the seal plate provides an interface between a void located between the shield and the backing and a breach detector. The breach detector is configured to detect pressure, volume, moisture or mass deviations in fluid disposed in the void, and the deviations indicate whether there's a rupture in the shield or the backing. The breach detector can be connected to an alarming device or signaling system to provide warnings and alerts to valve operators, process control panels or data communication networks.

Abstract: A thermodynamically controlled process for preparing Form I polymorph of lamivudine is described, wherein the process involves crystallizing Form I at a temperature of from about 0° C. to about 50° C. from a mixture which comprises (a) lamivudine or an acid salt thereof or both, (b) a solvent system comprising water and at least one organic solvent, and optionally (c) Form I seed; wherein, when a lamivudine acid salt is employed in the mixture, the crystallizing step is conducted in the presence of a base; and wherein the water activity of the solvent system is maintained in a range in which Form I is thermodynamically the most stable form of lamivudine.

Abstract: Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Abstract: A method is described for producing protein compositions having reduced amounts of O-linked glycosylation. The method includes producing the protein in cells cultured in the presence of an inhibitor of Pmt-mediated O-linked glycosylation and/or in the presence of one or more ?-1,2-mannosidases.

Abstract: Compounds of Formula I: I (where variables R1A, R1B, R2, R3, R4, A, and Z are as defined herein) useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP receptors are involved.

Abstract: Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Abstract: The invention provides compounds 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: This invention relates to deuterated compounds which are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

Abstract: The invention relates to kisspeptide-pentasaccharide conjugates having the general formula (I) wherein Z1 is Tyr or D-Tyr; Z3 is Trp, Hyp, Phe or Lys(R2); Z5 is Thr, Aib or Ala; Z7 is Gly or azaGly; Z8 is Leu; or Z7 and Z8 together represent; Z10 is Phe or Trp; n is 0 or 1; or R2, when present, represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SO3X; X is a positively charged counterion; with the proviso that when R2 is present, R1 is H or (C1-6) alkylcarbonyl; R3 is H or (C1-3)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same as well as to the use of said kisspeptide-pentasaccharide conjugates in the treatment of female infertility.

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to ?-amyloid (A?) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination nation with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (A?) protein, including Alzheimers disease, are also disclosed.