Abstract: The present invention provides a novel synthesis of verubecestat, and two novel crystalline forms of verubecestat, as well as pharmaceutically acceptable compositions thereof, each of which may be useful in treating, preventing, ameliorating, and/or delaying the onset of an A? pathology and/or a symptom or symptoms thereof. Non-limiting examples of such A? pathologies, including Alzheimer's disease, are disclosed herein.

Abstract: Methods of treating proliferative disorders are described. In particular, combination treatment with a GITR agonist and a PD-1 antagonist are provided.

Abstract: The present invention is directed to a biochemical assay for simultaneous genomic and proteomic analysis.

Abstract: The present invention is directed to phenylcyanoquinolinone compounds which may be useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 9 (PDE9). 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: The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

Abstract: This disclosure relates to the treatment of intrapulmonary bacterial infections, including treatment of nosocomial pneumonia lung infections with pharmaceutical compositions containing the cephalosporin ceftolozane.

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: The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.

Abstract: Described herein are polymeric nanoparticles that comprise 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]-triazolo-[3,4-fJ[1,6]-naphthyridin-3-one (Compound A), or a pharmaceutically acceptable salt thereof, and methods of making and using such nanoparticles. The nanoparticle comprises about 50 to about 99.8 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic acid-co-glycolic acid)-poly(ethylene)glycol copolymer, wherein the total amount of poly(ethylene)glycol in the nanoparticle is about 10 to about 30 weight percent poly(ethylene)glycol and about 0.2 to about 30 weight percent of Compound A.

Abstract: A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed are compounds having the structure of Formula I, or a pharmaceutically acceptable salt of any thereof, wherein: “Z”, R1 and R2 are defined herein, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.

Abstract: The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, m, R1, R2, R3, R3, R3, R4, R5 and R9 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocycle Derivative, and methods of using the Fused Tricyclic Heterocycle Derivatives for treating or preventing HIV infection in a subject.

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

Abstract: The present invention is directed to piperidine isoxazole and isothiazole orexin compounds which are antagonists of orexin receptors. Such compounds are of the general structural formula I: wherein the variables are defined herein. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: The present invention provides four crystalline forms of verubecestat, as well as pharmaceutically acceptable compositions thereof, each of which may be useful in treating, preventing, ameliorating, and/or delaying the onset of an A? pathology and/or a symptom or symptoms thereof. Non-limiting examples of such A? pathologies, including Alzheimer's disease, are disclosed herein.

Abstract: Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the general formula (I) detailed within.

Abstract: Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, wherein D1, D2 and D3 are each N, CH, or substituted CH, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.

Abstract: The present invention is directed to pyrazole, triazole and tetrazole compounds which are antagonists of orexin receptors. Such compounds are of the general structural formula I: The present invention is also directed to uses of the compounds described herein in the potential 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: Disclosed are compounds of Formula G1: where “RG3”. “Rd1” to “Rd4”, “n”, “m”, “p”, “W”, “X”, “Y”, and “Z” are defined herein, which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2A receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

Abstract: Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.