Abstract: The compositions and methods described herein are directed to treating solid tumors using CAR T therapy. For example, the compositions include CAR T cells comprising an extracellular domain that binds OR2I1P, LY6G6D, LRRC15, LY6K, GCC, GFRA4, F2RL2, QRFPR, IQGAP3, SIGLEC15, HAVCR1, PSG9, KISS1R, PRAME, HCN4, DPEP3, TMEM270, HER2, SLC7A3, SPRR2F, SLC45A2, CHRM1, CHRNA2, STEAP1B, FCRL2, Luteinizing hormone receptor, EDB, or CLDN18.2.

Abstract: A liquid pharmaceutical composition for the treatment of an epilepsy disorder comprising clemizole HCl, a solvent, a preservative, and glycerol. The preservative and the clemizole HCl are stable during storage. The preservative comprises at least one of methyl parahydroxybenzoate, or ethyl parahydroxybenzoate. The solvent is a citrate buffer and the liquid pharmaceutical composition has a pH of 4 to 5. A method of preparing the liquid pharmaceutical composition by dissolving the clemizole HCl, the preservative, and the excipients in at least one of the solvent, a solubilizer, or a combined solvent-solubilizer solution. The method further comprises adding glycerol and adjusting the pH to 4 to 5. A method of treating a subject having an epilepsy disorder comprising administering the liquid pharmaceutical composition.

Abstract: This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) (“Degrons”), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.

Abstract: The invention provides a bifunctional compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, Cy1, Cy2, Cy3, Cy4, Z1, Z2 and the degron are as described herein.

Abstract: Provided herein, inter alia, are compounds, pharmaceutical compositions and methods related to the treatment of viral infections caused by coronavirus or enterovirus. Provided herein are compounds of Formula (I), (II) and (III) and methods of using the compounds for therapy. These compounds are peptidomimetics that inhibit protease 3CL of a coronavirus, and are useful for treating conditions caused by viral infections, including COVID-19.

Abstract: Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors or additional cells in combination therapies.

Abstract: The present disclosure relates to: a) crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b) pharmaceutical compositions comprising one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, and, optionally, one or more pharmaceutically acceptable carriers; c) methods of treating a tumor a cancer, or a Rasopathy disorder by administering one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof; and methods of producing essentially pure Form IV of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide.

Abstract: Provided are methods of producing Active Pharmaceutical Ingredient (API) grade migalastat hydrochloride, and for purifying intermediate grade migalastat hydrochloride. Further provided are methods of producing [(2R,3S,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride (lucerastat hydrochloride) and other 1-deoxygalactonojirimycin compounds, as well as methods of purifying intermediate grade lucerastat hydrochloride and other 1-deoxygalactonojirimycin compounds.

Abstract: Aspects of the present disclosure are directed to systems, methods, and computer readable media for regulating digital therapeutic content for provision. A computing system may identify a digital therapeutic content to be provided via a network. The computing system may apply the digital therapeutic content to a machine learning (ML) model having a set of weights. The computing system may determine, from applying the digital therapeutic content to the ML model, an indication as of one of compliance or non-compliance. The computing system may store, using one or more data structures, an association between the digital therapeutic content and the indication used to control provision of the digital therapeutic content via the network, by (i) restricting the digital therapeutic content from provision responsive to determining the indication of non-compliance and (ii) permitting the digital therapeutic content to be provided responsive to determining the indication of compliance.

Abstract: The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifin, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.

Abstract: A method for preparing a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical using a selective azide substitution reaction includes (1) obtaining a [18F]fluoride from a cyclotron through an 18O(p,n)18F reaction; (2) separating the [18F] fluoride using an acetonitrile reaction solution containing dissolved K2,2,2 and K2CO3 to obtain a [18F]F?/H218O solution; (3) heating the [18F]F?/H218O solution to obtain K2,2,2/K18F; (4) placing the K2,2,2/K18F along with a bis(tosyloxy)methane compound into a reactor and adding a reaction solvent to cause a reaction and obtain a first precursor solution; (5) cooling the first precursor solution and adding an azide reagent to cause an azide substitution reaction and obtain a [18F]fluoromethyltosylate compound; (6) adding a bioactive molecule to the [18F]fluoromethyltosylate compound to cause an alkylation reaction and obtain a second precursor solution; and (7) adding a precursor scavenger to the second precursor solution and scavenging unreacted precursors to p

Abstract: Agents, kits, and methods that utilize oxygenation to prevent and/or treat intestinal inflammation and/or infections caused by anaerobic microorganisms are provided. In several embodiments, the formulations are provided as a capsule within a capsule in order to separate an oxygen prodrug from a catalyst until the formulation is at a target site within the intestine. In several embodiments, the catalyst is provided in an excess of the oxygen prodrug. In several embodiments, the prodrug is within an inner capsule or coating and a biological material comprising a catalyst (e.g., yeast, spirulina, chlorella, etc.) surrounds the encapsulated prodrug and the biological material is within a capsule or coating. The agents, kits, and methods can be utilized to prevent and/or treat anaerobic bacterial infections of the intestinal lumen by enteric aerobization therapy.

Abstract: The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

Abstract: Provided herein are systems and methods for simulating testing environments for digital therapeutic applications to address conditions over spans of time. A computing system may select a trigger from a plurality of triggers of an event scheduler for addressing a condition. The computing system may set a clock to a timestamp of the trigger, wherein the clock is accessible to the service and to the user device. The computing system may cause the service to transmit a message for addressing the condition to the user device, responsive to the timestamp of the clock corresponding to the timestamp of the trigger. The computing system may identify that the message is communicated between the service and the user device in accordance with the trigger. The computing system may determine that the trigger of the event scheduler is validated, responsive to identifying that the message is communicated.

Abstract: Provided herein are compositions, methods of making the same, and methods for targeted delivery of therapeutic agents for modifying expression and function of target genes, e.g. proteins involved in lipid and cholesterol metabolism such as PCSK9. Further provided herein are compositions and methods of treating conditions related to coronary disease.

Abstract: Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: Formula (I), wherein the substituents are as described.

Abstract: The disclosure features fusion proteins that are conditionally active variants of IL-12. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling.

Abstract: Provided herein are methods of treating nalbuphine-treatable disorders in a hepatically impaired patient.

Abstract: The present invention provides codon optimized Factor IX sequences, vectors and host cells comprising codon optimized Factor IX sequences, polypeptides encoded by codon optimized Factor IX sequences, and methods of producing such polypeptides. The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor IX nucleic acid sequence or the polypeptide encoded thereby.

Abstract: The present disclosure relates to novel processes for the preparation of compounds of Formula I. Some of these compounds are useful as stimulators of soluble guanylate cyclase (sGC). Others are useful intermediates towards the preparation of said stimulators. These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl) pyrazoles of Formula I in high purity and yields. The present invention has the additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides novel intermediates useful in the preparation of said compounds.