Abstract: The invention provides methods for overcoming glucocorticoid resistance of cancers by inhibition of CASP1. Also disclosed are diagnostic methods for determining glucocorticoid resistance potential by measuring expression level or promoter methylation status of CASP1 gene and/or NLRP3 gene.

Abstract: The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.

Abstract: Provided are compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: Fusion Protein compositions comprising masked IFNs and methods of making masked IFNs are disclosed herein. Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease.

Abstract: This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3?-deoxyadenosine-5?-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.

Abstract: The present invention provides a recombinant protein. The recombinant protein includes an anti-PD-1 antibody and human SIRPA extracellular domain. The N-terminus of the human SIRPA extracellular domain is linked to the C-terminus of the heavy chain of the anti-PD-1 antibody.

Abstract: The present disclosure relates to a gastrointestinal delivery device of a chitosan dressing, where the delivery device is capable of stop bleeding, in particular in connection with TURP procedures. The delivery device may be used in all gastrointestinal bleeding applications and can be used with a biocompatible, foldable, thin profile, chitosan dressing. Various aspects of the device and its uses are provided herein.

Abstract: The invention relates to the compounds or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula III, formula IV and formula V and the methods for the treatment of xerostomia may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of oral mucosal inflammatory, dry mouth or oral dry mouth mediated infectious diseases.

Abstract: The present invention provides means and methods for treating Interleukin 18 (IL-18)-associated diseases and disorders. In particular, the present invention discloses antibodies specific for free IL-18 and IL-18 Binding Protein (IL-18BP) for use in such treatments and for the diagnosis of the indications.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Human Respiratory Syncytial Virus (HRSV) or Human Metapneumovirus (HMPV) inhibitors. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HRSV or HMPV infection. The invention also relates to methods of treating an HRSV or HMPV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The invention provides novel classes of HCV therapeutics that are orally available, safe and effective HCV NS3/4A protease inhibitors and are less susceptible to drug resistance than existing therapeutics. The invention also relates to pharmaceutical composition of these compounds and methods of preparation and use thereof.

Abstract: Described herein are methods and compositions for treating diabetes mellitus, concerning oral pharmaceutical compositions comprising insulin in combination with a GLP-1 analogue.

Abstract: Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.

Abstract: Disclosed in the present invention is a method for preparing a Y-branched hydrophilic polymer carboxylic acid derivative, in particular a method for preparing a Y-branched polyethylene glycol carboxylic acid derivative having a high purity and high molecular weight. The preparation steps are simple, the product of the reaction is easy to be separated, the cost for separation is low, and the purity and yield of the product are high, facilitating the subsequent preparation of other derivatives and medicament conjugates based on the preparation of the carboxylic acid derivative, which is advantageous for industrial scale-up and commercial applications. The prepared Y-branched hydrophilic polymer carboxylic acid derivative (in particular the Y-branched polyethylene glycol carboxylic acid derivative having a high molecular weight) product has a high purity and high commercial application value, in particular in the use of the preparation of medicaments for preventing and/or treating diseases.

Abstract: Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in Homo sapiens. The compounds are derivatives of cordycepin (3?-deoxyadenosine) having a 2? and/or 5?-amino-acid ester phosphoramidate moiety.

Abstract: The present disclosure provides a single dose form composition to optimize the relationship between the ‘Folate-Cobalamin’ and ‘Choline-Betaine’ pathways. Single dose form compositions disclosed herein ensure an adequate intake of the rate limiting compounds that have been demonstrated to reduce the efficiency of this vital metabolic axis, and methods of use thereof.

Abstract: An artificial intelligence (AI) system and methods for management of an autoimmune or inflammatory condition, disorder or disease in a patient for the diagnosis, prognosis, or risk assessment of symptoms thereof. The AI system includes patient and provider applications and a payer application interface accessible via a communications network. The system contains a data-driven recommendation engine using machine learning and/or deep learning based on active monitoring of patients with an autoimmune or inflammatory-related condition, disorder, or disease. The system can alert clinicians to an impending symptom flare and provide a treatment solution that reduces symptom severity, reduces or eliminates the onset.

Abstract: The present disclosure relates to constructs useful in expressing biotinylated monomers and tetramers produced from these monomers. Specifically, the disclosure provides a construct useful in expressing biotinylated antigen monomers, said construct comprising a viral protein of an ectodomain of Hepatitis C Virus (HCV) envelope glycoprotein E2 or Human Immunodeficiency Virus (HIV) gp140. Further disclosed are methods for production and use of these tetramers in identifying and isolating antigen specific B cells and cloning antibodies thereto.

Abstract: The present invention relates to a stabilized pharmaceutical preparation of R27T, the preparation comprising a human interferon beta variant (R27T), an acetate buffer, arginine, trehalose, Poloxamer 188, and methionine. The stabilized R27T pharmaceutical preparation according to the present invention is obtained by the development of a preparation having a novel composition through the substitution of mannitol with trehalose in the composition of a preparation containing mannitol, which was previously studied by the present inventors.

Abstract: The present disclosure provides processes for the preparation of a compound of formula: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates.

Abstract: The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.

Abstract: The present invention provides pharmaceutical compositions and methods for preventing, delaying onset of, or treating diseases or disorders associated with cortico-hippocampal hyperactivity such as epilepsy, using an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system, optionally together with a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof.

Abstract: Compositions, kits and methods for assessing the presence of pathological fibroblasts within a biological sample are provided. In addition, compositions, kits and methods for detecting fibrosis are provided. Also provided are methods for treating fibrosis and conditions characterized with pathological fibroblasts.

Abstract: The present application belongs to the field of chemical synthesis, and specifically relates to a six-membered ring-containing nucleoside compound and a preparation method thereof. The present application discloses a six-membered ring-containing nucleoside compound. The structural formula of the nucleoside compound 7 is: where R1 is selected from one of where R2 is hydroxyl or alkynyl.

Abstract: Provided are compounds of Formula I, as well as pharmaceutical compositions containing compounds of Formula I and methods for treating Orthomyxoviridae virus infections by administering these compounds. The compounds, compositions, and methods provided are particularly useful for the treatment of Human Influenza virus infections.

Abstract: A pharmaceutical composition comprising (i) a therapeutically effective amount of an inhibitor of the oncogene SLC29A2; and (ii) a pharmaceutically acceptable carrier, for use in suppressing proliferation, occurrence, and metastasis of cancer cells overexpressing the oncogene SLC29A2 in a cancer patient, and/or prolonging cancer patient survival. The inhibitor of the oncogene SLC29A2 may be at least one selected from the group consisting of dipyridamole, dilazep, draflzine, nitorbenzylthioinosine, and the derivatives thereof. The composition for use may further comprise sorafenib for the same use.

Abstract: Disclosed are pharmaceutical compositions comprising three antiviral compounds. In particular, the pharmaceutical compositions comprise an effective amount of velpatasvir, an effective amount of sofosbuvir, and an effective amount of voxilaprevir. Also disclosed are methods of use for the pharmaceutical composition.

Abstract: The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

Abstract: A compostable biopolymer adhesive may include a starch, a hydroxylic liquid, a preservative mixture, a crystallization inhibitor, and a carbonate, wherein the compostable biopolymer may be free of synthetic materials yet has a long shelf life, is stable at room temperature, and which can be used to make slime for play.

Abstract: The present invention generally relates to dietary supplement and pharmaceutical formulations comprising layered acid protective oral dosage formulations comprising probiotics and provided as single unified or cohesive dosage form units. Each individual acid protective layer of the cohesive dosage form provides one of a different probiotic payload, a different release profile to target delivery of probiotic to a particular region in the gastrointestinal tract, or both different probiotic payloads and release profiles to target delivery of different probiotics to particular regions in the gastrointestinal tract.

Abstract: The present invention relates to compounds of the formula (I), or pharmaceutically acceptable salts, enantiomer or diastereomer thereof, wherein R1 to R5 are as described above. The compounds may be useful for the treatment or prophylaxis of hepatitis B virus infection.

Abstract: The present invention relates to a liquid formulation containing botulinum toxin and stabilizing agent, and preparation method therefor. A liquid formulation containing botulinum toxin and stabilizing agent according to the present invention be can be easily stored and distributed. It was proved a significant effect on the stabilization of botulinum toxin under suitable conditions according to the temperature and pH of the human body. Thus, it is expected that the pharmaceutical composition of the present invention will greatly contribute to the safe and convenient medical use of botulinum toxin.

Abstract: The present invention provides a preparation method for PCV2 capsid protein and a pharmaceutical composition containing said capsid protein. The method of the present invention uses a novel arabinose-induced expression vector and thereby improves the synthesis efficiency of said PCV2 capsid protein. On the other hand, the present pharmaceutical composition combines said capsid protein and other favorable components at a proper ratio so that achieves excellent immune-inducing effects.

Abstract: A compound represented by the following formula (1) is provided: wherein X represents a sulfur atom or —CH?CH—; A1 to A4 each independently represent a carbon atom or a nitrogen atom, and at least one of A1 to A4 is a nitrogen atom; R1 represents any one of a 1,2,3,4-tetrahydroquinolyl group (or a 3,4-dihydro-1(2H)-quinolyl group), a 3,4-dihydro-4,4-dimethyl-1(2H)-quinolyl group, a 2,3,4,5-tetrahydro-1H-1-benzazepinyl group, or a substituent represented by the following formula (2): wherein R4 represents a 2,3,4-trifluorophenyl group, a 4-iodophenyl group, a 2,3-difluorophenyl group, a 3,5-difluorophenyl group, a 5-fluoro-2-methylphenyl group, a 3-pentafluorosulfanylphenyl group, a 2,6-dimethylphenyl group, a 4-benzyloxyphenyl group, a 3,5-bis(trifluoromethyl)biphenyl group, a 4-tert-butylphenyl group, a 3-methoxyphenyl group, an unsubstituted or substituted pyridyl group, or an unsubstituted or substituted naphthyl group; R5 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a l

Abstract: Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein, produce a synergistic effect on the inhibition of HCV polymerase.

Abstract: The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.

Abstract: A comestible dosage form article for administration to a target subject, the dosage form comprising: an outer capsule comprising a first cap telescopically engageable with a first body; and an inner capsule, within the outer capsule, comprising a second cap telescopically engageable with a second body, wherein the inner capsule is inverted with respect to the outer capsule such that, in an assembled state, the second cap is proximal to the first body and distal to the first cap.

Abstract: A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.

Abstract: This invention relates the use of cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.

Abstract: The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.

Abstract: Described herein are methods and compositions for treating diabetes mellitus, concerning oral pharmaceutical compositions comprising insulin in combination with a GLP-1 analog.

Abstract: Compounds having the following formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, D, E and R1 are as defined herein, are provided. Methods comprising the use of such compounds for the treatment of neurological disorders, such as pantothenate kinase-associated neurodegeneration, and pharmaceutical compositions containing such compounds, and their use in the treatment of neurological disorders, also are provided.

Abstract: Methods of inhibiting the growth of cells or inducing cell death by contacting the cells with or introducing into the cells a composition including a 5? triphosphate, 2? fluoro-modified pyrimidine non-linear single stranded RNA at least 17 nucleotides long with a least 3 base pairings or a 5? triphosphate, 2? fluoro-modified double stranded RNA at least 17 base pairs long in an amount effective to inhibit cell growth, induce cell death or induce cytokine production by the cells. The methods also include administration of the compositions to a subject. The subject may have a proliferative disorder or infectious disease and administration of the compositions provided herein may treat the disorder or disease.

Abstract: The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-?) mutant molecule. The engineered Ab-IFN-? mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-? fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-? fusion molecules.

Abstract: This invention relates the use of cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.

Abstract: The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.

Abstract: A method for enhancing infectivity of HCMV virus particles is provided.

Abstract: The invention features compositions and methods for site-specific modification of proteins by incorporation of an aldehyde tag. Enzymatic modification at a sulfatase motif of the aldehyde tag through action of a formylglycine generating enzyme (FGE) generates a formylglycine (FGly) residue. The aldehyde moiety of FGly residue can be exploited as a chemical handle for site-specific attachment of a moiety of interest to a polypeptide.

Abstract: Embodiments of the invention are directed to methods of diagnosing bacterial infection in a critically ill patient. The methods include obtaining a sample from the patient and determining the patient's level of IL-27 expression. Embodiments of the invention are also directed to methods that include determining both the patient's levels of IL-27 expression and PCT expression and using the combined result to provide a diagnosis of bacterial infection in a critically ill patient.