Thu, 25 Aug 2016 08:00:00 EDTSystems and methods for diagnosing acute kidney injury following an acute event or surgical intervention, based on assessing the biomarker L-FABP. Also, systems and methods for predicting the risk of an individual to suffer from a kidney injury after an acute event or surgical intervention in the future.
Thu, 25 Aug 2016 08:00:00 EDTCompositions and methods for identifying and treating patients having altered capacity for LC-PUFA production are disclosed.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides compositions and methods based on genetic polymorphisms that are associated with response to statin treatment (particularly for reducing the risk of venous thrombosis). For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.
Thu, 25 Aug 2016 08:00:00 EDTNetwork-based meta-analysis of four independent microarray studies identified the hepatocyte nuclear factor (HNF4A), a transcription factor associated with gluconeogenesis and diabetes, as a central regulatory hub gene upregulated in blood of PD patients. In parallel, the polypyrimidine tract binding protein 1 (PTBP1), involved in the stabilization and mRNA translation of insulin, was identified as the most downregulated gene. Using both markers, PD patients were classified with 90% sensitivity and 80% specificity. Longitudinal performance analysis demonstrated that relative abundance of HNF4A and PTBP1 mRNAs significantly decreased and increased, respectively, in PD patients during 3 years follow up period. The inverse regulation of HNF4A and PTBP1 provides a molecular rationale for the altered insulin signaling observed in PD patients. The longitudinally dynamic biomarkers identified in this study may be useful for monitoring disease-modifying therapies for PD.
Thu, 25 Aug 2016 08:00:00 EDTIncreasing evidence indicates that Parkinson's disease (PD) and type 2 diabetes (T2DM) share dysregulated molecular networks. 84 genes shared between PD and T2DM were identified from curated disease-gene databases. Nitric oxide biosynthesis, lipid and carbohydrate metabolism, insulin secretion and inflammation were identified as common dysregulated pathways. A network prioritization approach was implemented to rank genes according to their distance to seed genes and their involvement in common biological pathways. This disclosure reinforces the idea that shared molecular networks between PD and T2DM provide an additional source of biologically meaningful biomarkers.
Thu, 25 Aug 2016 08:00:00 EDTCompositions and methods for the detection and treatment of autism and autistic spectrum disorder are provided.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides genotyping methods and compositions for selecting patients with cardiovascular disease who will benefit from treatment with HDL-raising or HDL mimicking agent, in particular with a CETP inhibitor/modulator.
Thu, 25 Aug 2016 08:00:00 EDTThe invention described herein provides for methods and systems for determining, selecting, and/or treating diseases and conditions caused by or associated with high quantities of methanogens in a subject, or diseases and conditions caused by or associated with low quantities of methanogens in a subject. In various embodiments, a therapy to inhibit the growth of methanogens or to promote the growth of methanogens are selected and/or administered to a subject in need thereof.
Thu, 25 Aug 2016 08:00:00 EDTMethods for treating Alzheimer's Disease (AD) using modulators of lysosomal activity are described herein. More particularly, methods described herein relate to the use and application of compounds or agents that enhance lysosomal activity for the treatment of AD. In a particular aspect, the method relates to the use and application of compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD. Also described herein are methods and assays for screening to identify compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure relates to a method for treatment or prevention of diseases have an increased level of insulin-like growth factor I (IGF-I). The method comprises administration of a growth hormone (GH) variant having antagonistic activity in combination with an oligonucleotide targeted to growth hormone receptor (GHR) to a subject in need.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure relates generally to compounds comprising oligonucleotides complementary to a cystic fibrosis transmembrane conductance regulator (CFTR) RNA transcript. Certain such compounds are useful for hybridizing to a CFTR RNA transcript, including but not limited to a CFTR RNA transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the CFTR transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with Cystic Fibrosis.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.
Thu, 25 Aug 2016 08:00:00 EDTDisclosed herein are methods, compositions, polynucleic acid polymers, assays, and kits for inducing processing of a partially processed mRNA transcript to remove a retained intron to produce a fully processed mRNA transcript that encodes a full-length functional form of a protein. Also described herein are methods and compositions for treating a disease or condition characterized by impaired production of a full-length functional form of a protein or for treating a disease or condition characterized by a defective splicing in a subject.
Thu, 25 Aug 2016 08:00:00 EDTAnti-cadherin and anti-ZO-1 agents and compositions, and kits containing them for use in the promotion and/or improvement of wound healing and/or tissue repair, and for anti-scarring, anti-inflammatory, anti-fibrosis and anti-adhesion indications.
Thu, 25 Aug 2016 08:00:00 EDTMethods for malignant glioma diagnosis/prognosis using miR-138 as a prognostic biomarker and methods for treating malignant glioma and inhibiting glioma stem cell growth by suppressing miR-138. Also disclosed herein are pharmaceutical compositions for use in treating malignant glioma, prolonging survival of malignant glioma patients, or eliminating GSCs and in turn tumor growth, the pharmaceutical composition comprising an oligonucleotide that targets miR- 138.
Thu, 25 Aug 2016 08:00:00 EDTThe invention is directed to compositions and methods for treating or reducing the likelihood of the development of epilepsy in an individual. The method comprises administering to the central nervous system of an individual in need of such treatment a therapeutically effective amount of an agent capable of increasing the expression and/or activity of miR-128.
Thu, 25 Aug 2016 08:00:00 EDTThe disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand; the two strands form a duplex with at least one blunt end; and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker; and a 3 end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3 end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optionally, the first or second strand is the sense strand, and the sense strand can comprise a 5 end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.
Thu, 25 Aug 2016 08:00:00 EDTMethods of regulating PGC1α and/or PGC1β, or treating diseases associated with PGC1α and/or PGC1β using a miR-130a RNA, miR-130b RNA, or a combination thereof, or using an antagomiR of miR-130a, an antagomiR of miR-130b, or both, which can be in the form of microRNA sponge or a locked nucleic acid (LNA).
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure relates to the finding that microRNA-155 plays a role in inflammation, hematopoiesis and myeloproliferation, and that dysregulation of microRNA-155 expression is associated with particular myeloproliferative disorders. Disclosed herein are methods and compositions for diagnosing an treating disorders, including inflammation and myeloproliferation, modulating the levels of expression of one or more genes selected from the group consisting of Cutl1, Arnt1, Picalm, Jarid2, PU.1, Csf1r, HIF1α, Sla, Cepbβ, and Bach1, and the like.
Thu, 25 Aug 2016 08:00:00 EDTDescribed herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modification patterns that yield potent inhibitors of miR-21 activity. The compositions may be used to inhibit miR-21, and also to treat diseases associated with abnormal expression of miR-21, such as fibrosis and cancer.
Thu, 25 Aug 2016 08:00:00 EDTThe technology described herein relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the Serpina1 gene, and methods of using such dsRNA compositions to inhibit expression of Serpina1.
Thu, 25 Aug 2016 08:00:00 EDTThis disclosure describes non-naturally occurring protein scaffolds and methods of making and using the protein scaffolds. In one aspect, therefore, this disclosure describes a non-naturally occurring protein scaffold that includes a plurality of structural domains and a plurality of loop regions that include an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, substitution, or addition. Generally, the structural domain or domains can include at least one β structure and/or at least one a helix.
Thu, 25 Aug 2016 08:00:00 EDTC-terminal endostatin polypeptides are disclosed herein. Polynucleotides encoding these polypeptide, host cells transformed with the polynucleotides, and methods of using these polypeptides and polynucleotides are disclosed. Uses of these polypeptide, polynucleotides and expression vectors include the treatment of fibrosis in a subject. Thus, methods are provided for treating fibrosis, including fibrosis of the skin and/or the lung.
Thu, 25 Aug 2016 08:00:00 EDTOphthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has an amino acid sequence of SEQ ID NO:4.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotide molecules encoding at least one polypeptide of interest to modulate the immune response.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotide molecules encoding low density lipoprotein receptor comprising at least one mutation (e.g., an LDLR signally enhancing mutation).
Thu, 25 Aug 2016 08:00:00 EDTThe present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor. The invention is further directed to the consensus sequences for use in engineering a synthetic tissue protective peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.
Thu, 25 Aug 2016 08:00:00 EDTThe invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
Thu, 25 Aug 2016 08:00:00 EDTThis invention relates to collagen-binding synthetic peptidoglycans and engineered collagen matrices comprising a collagen matrix and a collagen-binding synthetic peptidoglycan where the collagen-binding synthetic peptidoglycan can be aberrant or can have amino acid homology with a portion of the amino acid sequence of a protein or a proteoglycan that regulates collagen fibrillogenesis. The invention also relates to kits, compounds, compositions, and engineered graft constructs comprising such collagen-binding synthetic peptidoglycans or engineered collagen matrices and methods for their preparation and use.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides inventive stabilized STAT polypeptides, pharmaceutical compositions thereof and methods of making and using inventive stabilized STAT polypeptides.
Thu, 25 Aug 2016 08:00:00 EDTThe invention concerns peptides useful as MAP kinase/ERK pathway-specific inhibitors relative to a given substrate in a given subcellular compartment.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to an Aβ modulating peptide comprising a peptide selected from the list of peptides comprising: (i) Arg-Lys-Leu-Met-Gln-Pro-Thr-Arg-Asn (SEQ ID NO:1); (ii) Arg-Lys-Leu-Met-Gln-Pro-Thr-Arg-Asn-Arg-Arg-Asn-Pro-Asn-Thr (SEQ ID NO:2); (iii) a peptide according to (i) or (ii) wherein at least one of the amino acids is a D-amino acid; (iv) a functional variant of a peptide according to any one of (i) to (iii); and (v) a peptide consisting of at least 3-5 contiguous amino acid residues of a peptide according to (i), (ii), (iii) or (iv). The present invention also relates to an Aβ modulating peptide comprising SEQ ID NO: 2 wherein all of the amino acids are D-amino acids.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to tripeptide compounds according to the general formula (1) and their use as a medicament, in particular as anti-inflammatory agents.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure provides a method for extracting a soluble protein from a population of microorganisms, the method comprising contacting the population of microorganisms expressing the soluble protein with an amount of a solution comprising from about 1% (v/v) to less than 50% (v/v) carboxylic acid effective to extract the soluble protein from the population of microorganisms.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to digoxin and digitoxin derivatives that are selective inhibitors of the α2 isoform of Na,K-ATPase, and that reduce intra-ocular pressure. The invention further relates to uses of these derivatives for treating disorders associated with elevated intraocular pressure, such as glaucomas, and/or as cardiotonic agents.
Thu, 25 Aug 2016 08:00:00 EDTA compound of formula (I) wherein Ar can be one six-membered or two fused six-membered aromatic rings; R8 and R9 can be hydrogen, alkyl, cycloalkyl, halogens, amino, alkylamino, dialkylamino, nitro, cyano, alkyoxy, aryloxy, thiol, alkylthiol, arythiol, or aryl; Q can be O, S or CY2, where Y may be H, alkyl or halogens; X can be O, NH, S, N-alkyl, (CHR2)m where m is 1 to 10, and CY2; Z can be O, S, NH, or N-alkyl; U″ is H and U′ can be H or CH2; wherein: T can be OH, H, halogens, O-alkyl, O-acyl, O-aryl, CN, NH2 or N3; T′ and T″ can be H or halogen; and W can be H or a phosphate group. Compounds show anti-viral activity, for example with respect to varicella zoster virus.
Thu, 25 Aug 2016 08:00:00 EDTCompounds of the general formula (I): processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
Thu, 25 Aug 2016 08:00:00 EDTThe subject matter of the invention is novel 2′,5′-dideoxy-5-fluorouridine derivatives of general formula 1. wherein R1 denotes cinchona alkaloid fragment with defined absolute configuration at C-8 and C-9 atoms.In a second aspect, the subject matter of the invention is a process for the manufacture of 2′,5′-dideoxy-5-fluorouridine derivatives of general formula 1.In a third aspect, the subject matter of the invention is an application of 2′,5′-dideoxy-5-fluorouridine derivatives of general formula 1 in the anticancer treatment of breast cancer, cervical cancer, lung cancer and nasopharynx cancer.
Thu, 25 Aug 2016 08:00:00 EDTNew crystalline forms of macrolide compounds, and pharmaceutical compositions thereof, are described herein. In addition, processes for preparing the crystalline forms are described herein.
Thu, 25 Aug 2016 08:00:00 EDTThe invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of Formula I: wherein the variables are as defined herein.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides a compound of Formula II: or a pharmaceutically acceptable salt thereof.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to azole compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to novel phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor compounds of formula (I) and (II), which are conformationally restricted, and for which the meaning of the substituents are listed in the description. Preferred compounds are those wherein X isoxygen, R1 is morpholino and R2 is substituted phenyl or heteroaryl. These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to newer generation of triazoles, tetrazoles, isoxazoles, urea and sulphonamide functionalities containing 6-nitro-2, 3-dihydronitroimidazooxazoles agents of formula 1, their method of preparation, and their use as drugs for treating Mycobacterium tuberculosis, MDR-TB and XDR-TB either alone or in combination with other anti-tubercular agents. In the present invention, new generation 6-nitro-2, 3-dihydronitroimidazooxazoles agents also show acceptable pharmacokinetic properties and synergistic or additive effects with known anti-tubercular drugs.
Thu, 25 Aug 2016 08:00:00 EDTThe present application relates to novel 2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxamide derivatives (“thienouracil”-carboxamides), to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases and to their use for the preparation of medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of pulmonary and cardiovascular disorders.
Thu, 25 Aug 2016 08:00:00 EDTThis invention relates to opioid ketal compounds of Formula (I), Formula (II), or Formula (III): or a pharmaceutically acceptable salts thereof, wherein R1 is H or CH3, R2 is H or OH, n is 0, 1, 2 or 3, R3 and R4 are independently H or optionally substituted C1-C4 alkyl, or when n is 0, then R3 and R4 and the carbon atoms to which they are attached together form six, or seven membered ring, which is optionally mono or disubstituted by C1-C4 alkyl. The invention also relates to oxycodone ketal compounds of Formula (IV) or (V): or a pharmaceutically acceptable salts thereof. The invention also relates to the use of such compounds for the treatment, prevention, or amelioration of pain.
Thu, 25 Aug 2016 08:00:00 EDTCrystals of a dispiropyrrolidine compound or a salt thereof which inhibits the action of Mdm2 are provided. The present invention provides crystals of (3′R,4′S,5′R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6″-chloro-4′-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2″-oxo-1″,2″-dihydrodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indole]-5′-carboxamide or a salt thereof which inhibits Mdm2 and has anti-tumor activity. The present invention also provides a medicament comprising the same.
Thu, 25 Aug 2016 08:00:00 EDTThe invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.
Thu, 25 Aug 2016 08:00:00 EDTDisclosed are chemical entities that inhibit ubiquitin-activating enzyme (UAE), each of which is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein Y is and W, Z, XY, RY1, RY2 and RY3 are defined herein; pharmaceutical compositions comprising the chemical entities; and methods of using the chemical entities. These chemical entities are useful for treating disorders, particularly cell proliferation disorders, including cancers.